Modeling and resistant alleles explain the selectivity of antimalarial compound 49c towards apicomplexan aspartyl proteases
Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptid...
Saved in:
Published in | The EMBO journal Vol. 37; no. 7 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
03.04.2018
Blackwell Publishing Ltd John Wiley and Sons Inc |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Toxoplasma gondii
aspartyl protease 3 (TgASP3) phylogenetically clusters with
Plasmodium falciparum
Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX. To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap‐like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15‐fold the IC
50
values of 49c. Compellingly the selection of mutagenized
T. gondii
resistant strains to 49c reproducibly converted F344 to a cysteine residue.
Synopsis
The apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX play pivotal roles in the lytic cycle of
Toxoplasma gondii
and
Plasmodium falciparum
. The anti‐malarial compound 49c is a selective peptidomimetic inhibitor of these proteases that blocks host cell invasion and egress.
Molecular homology and substrate docking models of the TgASP3, PfPMIX and PfPMX catalytic domains uncover conformational determinants responsible for distinct substrate recognition.
A conserved phenylalanine residue in the aspartyl protease flap region is responsible for the selective sensitivity to 49c.
Mutation of the conserved phenylalanine to tyrosine confers parasite resistance to 49c.
Chemically mutagenized parasites selected for resistance to 49c harbour a cysteine mutation at the conserved phenylalanine residue, confirming its critical role.
Graphical Abstract
A conserved phenylalanine residue in the flap region of apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX confers selective sensitivity to the peptidomimetic inhibitor 49c. |
---|---|
AbstractList | Toxoplasma gondii
aspartyl protease 3 (Tg
ASP
3) phylogenetically clusters with
Plasmodium falciparum
Plasmepsins
IX
and X (Pf
PMIX
, Pf
PMX
). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin
II
selectively targets Tg
ASP
3, Pf
PMIX
, and Pf
PMX
. To unravel the molecular basis for the selectivity of 49c, we constructed homology models of Pf
PMIX
, Pf
PMX
, and Tg
ASP
3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap‐like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to Tg
ASP
3, Pf
PMIX
, and Pf
PMX
models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15‐fold the
IC
50
values of 49c. Compellingly the selection of mutagenized
T. gondii
resistant strains to 49c reproducibly converted F344 to a cysteine residue. Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap-like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15-fold the IC50 values of 49c. Compellingly the selection of mutagenized T. gondii resistant strains to 49c reproducibly converted F344 to a cysteine residue. Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX. To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap‐like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15‐fold the IC 50 values of 49c. Compellingly the selection of mutagenized T. gondii resistant strains to 49c reproducibly converted F344 to a cysteine residue. Synopsis The apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX play pivotal roles in the lytic cycle of Toxoplasma gondii and Plasmodium falciparum . The anti‐malarial compound 49c is a selective peptidomimetic inhibitor of these proteases that blocks host cell invasion and egress. Molecular homology and substrate docking models of the TgASP3, PfPMIX and PfPMX catalytic domains uncover conformational determinants responsible for distinct substrate recognition. A conserved phenylalanine residue in the aspartyl protease flap region is responsible for the selective sensitivity to 49c. Mutation of the conserved phenylalanine to tyrosine confers parasite resistance to 49c. Chemically mutagenized parasites selected for resistance to 49c harbour a cysteine mutation at the conserved phenylalanine residue, confirming its critical role. Graphical Abstract A conserved phenylalanine residue in the flap region of apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX confers selective sensitivity to the peptidomimetic inhibitor 49c. Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX. To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap‐like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15‐fold the IC50 values of 49c. Compellingly the selection of mutagenized T. gondii resistant strains to 49c reproducibly converted F344 to a cysteine residue. Synopsis The apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX play pivotal roles in the lytic cycle of Toxoplasma gondii and Plasmodium falciparum. The anti‐malarial compound 49c is a selective peptidomimetic inhibitor of these proteases that blocks host cell invasion and egress. Molecular homology and substrate docking models of the TgASP3, PfPMIX and PfPMX catalytic domains uncover conformational determinants responsible for distinct substrate recognition. A conserved phenylalanine residue in the aspartyl protease flap region is responsible for the selective sensitivity to 49c. Mutation of the conserved phenylalanine to tyrosine confers parasite resistance to 49c. Chemically mutagenized parasites selected for resistance to 49c harbour a cysteine mutation at the conserved phenylalanine residue, confirming its critical role. A conserved phenylalanine residue in the flap region of apicomplexan aspartyl proteases TgASP3, PfPMIX and PfPMX confers selective sensitivity to the peptidomimetic inhibitor 49c. Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX. To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap‐like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15‐fold the IC50 values of 49c. Compellingly the selection of mutagenized T. gondii resistant strains to 49c reproducibly converted F344 to a cysteine residue. aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting as key maturases for secreted proteins implicated in invasion and egress. A potent antimalarial peptidomimetic inhibitor (49c) originally developed against Plasmepsin II selectively targets TgASP3, PfPMIX, and PfPMX To unravel the molecular basis for the selectivity of 49c, we constructed homology models of PfPMIX, PfPMX, and TgASP3 that were first validated by identifying the determinants of microneme and rhoptry substrate recognition. The flap and flap-like structures of several reported Plasmepsins are highly flexible and critically modulate the access to the binding cavity. Molecular docking of 49c to TgASP3, PfPMIX, and PfPMX models predicted that the conserved phenylalanine residues in the flap, F344, F291, and F305, respectively, account for the sensitivity toward 49c. Concordantly, phenylalanine mutations in the flap of the three proteases increase twofold to 15-fold the IC values of 49c. Compellingly the selection of mutagenized resistant strains to 49c reproducibly converted F344 to a cysteine residue. |
Author | Marq, Jean‐Baptiste Soldati‐Favre, Dominique Tessaro, Francesca Vahokoski, Juha Scapozza, Leonardo Kursula, Inari Mukherjee, Budhaditya |
AuthorAffiliation | 2 Pharmaceutical Biochemistry School of Pharmaceutical Sciences University of Lausanne University of Geneva CMU Geneva Switzerland 3 Department of Biomedicine University of Bergen Bergen Norway 1 Department of Microbiology and Molecular Medicine University of Geneva CMU Geneva 4 Switzerland |
AuthorAffiliation_xml | – name: 2 Pharmaceutical Biochemistry School of Pharmaceutical Sciences University of Lausanne University of Geneva CMU Geneva Switzerland – name: 3 Department of Biomedicine University of Bergen Bergen Norway – name: 1 Department of Microbiology and Molecular Medicine University of Geneva CMU Geneva 4 Switzerland |
Author_xml | – sequence: 1 givenname: Budhaditya orcidid: 0000-0002-1058-3620 surname: Mukherjee fullname: Mukherjee, Budhaditya organization: Department of Microbiology and Molecular Medicine, University of Geneva CMU – sequence: 2 givenname: Francesca surname: Tessaro fullname: Tessaro, Francesca organization: Pharmaceutical Biochemistry, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva CMU – sequence: 3 givenname: Juha surname: Vahokoski fullname: Vahokoski, Juha organization: Department of Biomedicine, University of Bergen – sequence: 4 givenname: Inari orcidid: 0000-0001-5236-7056 surname: Kursula fullname: Kursula, Inari organization: Department of Biomedicine, University of Bergen – sequence: 5 givenname: Jean‐Baptiste surname: Marq fullname: Marq, Jean‐Baptiste organization: Department of Microbiology and Molecular Medicine, University of Geneva CMU – sequence: 6 givenname: Leonardo orcidid: 0000-0003-1079-648X surname: Scapozza fullname: Scapozza, Leonardo email: leonardo.scapozza@unige.ch organization: Pharmaceutical Biochemistry, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva CMU – sequence: 7 givenname: Dominique orcidid: 0000-0003-4156-2109 surname: Soldati‐Favre fullname: Soldati‐Favre, Dominique email: dominique.soldati-favre@unige.ch organization: Department of Microbiology and Molecular Medicine, University of Geneva CMU |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29519896$$D View this record in MEDLINE/PubMed |
BookMark | eNqFkc1vEzEQxS1URD_gzA1Z4sIlre1d79ockEpVvtSKC5yt2c04deTYi-20jfjncUkJBQlxsjT-vac38w7JXogBCXnO2TGXQooTXA3LY8F4rxVr-0fkgLcdmwnWyz1ywETHZy1Xep8c5rxkjEnV8ydkX2jJtdLdAfl-GefoXVhQCHOaMLtcIBQK3qPHTPF28uACLVdIc52MxV27sqHRVkFxK_CQHHg6xtUU19Wi1SMt8QbSPFOY3N3c4y0ECnmCVDaeTikWhIz5KXlswWd8dv8eka_vzr-cfZhdfH7_8ez0YjZK3vQzpYdhbLGZDwqsQsmllba1DMCKvgeFjR6gFUxb7EerceCd7aFrZNOpDrhujsibre-0HlY4HzGUBN5MqcZPGxPBmT9_grsyi3htpFK8a0Q1eHVvkOK3NeZiVi6P6D0EjOts6v2F5krJpqIv_0KXcZ1CXa9SNaPolVCVOtlSY4o5J7S7MJyZn8Wau2LNrtiqePFwhx3_q8kKvN4CN87j5n9-5vzy7aeH7mwrzlUXFph-p_5XoB-FwsXH |
CitedBy_id | crossref_primary_10_1016_j_biochi_2018_07_002 crossref_primary_10_3390_molecules25122749 crossref_primary_10_1021_acs_jmedchem_2c01336 crossref_primary_10_1021_acsmedchemlett_3c00404 crossref_primary_10_1002_cmdc_202200306 crossref_primary_10_1016_j_chom_2020_03_015 crossref_primary_10_1002_jcb_28062 crossref_primary_10_3390_pathogens10091128 crossref_primary_10_1021_acs_jcim_1c00840 crossref_primary_10_1074_jbc_REV120_009309 crossref_primary_10_1002_pro_4279 |
Cites_doi | 10.1371/journal.pone.0142509 10.7554/eLife.10809 10.1016/j.jsb.2011.04.009 10.1093/bioinformatics/btq662 10.1371/journal.ppat.1005211 10.1021/jm5014133 10.1126/science.8469986 10.1038/srep31420 10.1016/j.drudis.2013.10.027 10.1038/nsmb.3061 10.1021/ci400128m 10.1073/pnas.0508452103 10.1016/S0166-6851(99)00035-3 10.1021/ml4004952 10.2174/156802612799362959 10.1146/annurev.micro.62.081307.162802 10.1016/j.ijpara.2010.02.014 10.1021/ci800324m 10.1007/978-1-59745-196-3_14 10.1242/jcs.115.3.563 10.1016/j.str.2007.01.015 10.1186/1471-2164-15-354 10.1126/science.1074553 10.7554/eLife.27480 10.1016/S0166-6851(03)00119-1 10.1126/science.aaf8675 10.12688/f1000research.7924.1 10.1073/pnas.93.19.10034 10.1016/j.ijpara.2012.08.004 10.1038/nmeth.2857 10.1126/science.aan1478 10.1021/jm030644s 10.1038/nature08728 10.1110/ps.25801 10.1016/S0140-6736(04)16412-X 10.1016/j.bmcl.2012.11.118 10.1074/jbc.271.24.14010 10.1083/jcb.152.3.563 10.1016/S1471-4922(01)02037-2 10.1016/S0022-2836(03)00036-6 10.1021/cr010167q 10.1017/S0031182009006349 10.1016/j.meegid.2012.08.012 10.1039/C4MB00631C 10.1128/AAC.50.2.639-648.2006 10.1107/S2053230X15022049 10.1007/s11908-017-0583-8 10.1111/j.1600-0854.2007.00589.x 10.1007/s10822-013-9644-8 |
ContentType | Journal Article |
Copyright | The Author(s) 2018 2018 The Authors 2018 The Authors. 2018 EMBO |
Copyright_xml | – notice: The Author(s) 2018 – notice: 2018 The Authors – notice: 2018 The Authors. – notice: 2018 EMBO |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 7QG 7QL 7QP 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 K9. M7N P64 RC3 7X8 5PM |
DOI | 10.15252/embj.201798047 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Virology and AIDS Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database Nucleic Acids Abstracts ProQuest Health & Medical Complete (Alumni) Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management Genetics Abstracts Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Immunology Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic Virology and AIDS Abstracts MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Chemistry Biology |
DocumentTitleAlternate | Budhaditya Mukherjee et al |
EISSN | 1460-2075 |
EndPage | n/a |
ExternalDocumentID | 10_15252_embj_201798047 29519896 EMBJ201798047 |
Genre | article Research Support, Non-U.S. Gov't Journal Article |
GrantInformation_xml | – fundername: Swiss National Science Foundation grantid: FN3100A0‐116722; IZLIZ3‐156825 funderid: 10.13039/501100001711 – fundername: Academy of Finland grantid: 292718 funderid: 10.13039/501100002341 – fundername: Carigest SA – fundername: HHMI funderid: 10.13039/100000011 – fundername: EMBO Fellowship funderid: 10.13039/100004410 – fundername: Swiss National Science Foundation funderid: FN3100A0‐116722; IZLIZ3‐156825 – fundername: Academy of Finland funderid: 292718 – fundername: EMBO Fellowship – fundername: HHMI – fundername: Howard Hughes Medical Institute – fundername: Swiss National Science Foundation grantid: FN3100A0‐116722; IZLIZ3‐156825 – fundername: Academy of Finland grantid: 292718 |
GroupedDBID | --- -DZ -Q- -~X 0R~ 123 1OC 24P 29G 2WC 33P 36B 39C 53G 5VS 70F 8R4 8R5 A8Z AAESR AAEVG AAHBH AAHHS AAIHA AANLZ AAONW AASGY AAXRX AAZKR ABCUV ABJNI ABLJU ACAHQ ACCFJ ACCZN ACGFO ACGFS ACNCT ACPOU ACPRK ACXBN ACXQS ADBBV ADEOM ADKYN ADMGS ADOZA ADXAS ADZMN AEEZP AEGXH AEIGN AENEX AEQDE AEUYR AFBPY AFFNX AFGKR AFPWT AFRAH AFZJQ AHMBA AIAGR AIURR AIWBW AJBDE ALAGY ALIPV ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR AMYDB AOIJS AUFTA AZBYB AZFZN AZVAB BAWUL BDRZF BENPR BFHJK BMNLL BMXJE BRXPI BTFSW C6C CS3 DCZOG DIK DPXWK DRFUL DRSTM DU5 E3Z EBD EBLON EBS EJD EMB EMOBN ESTFP F5P G-S GROUPED_DOAJ GX1 HH5 HK~ HYE KQ8 LATKE LEEKS LITHE LOXES LUTES LYRES MEWTI MRFUL MRSTM MSFUL MSSTM MVM MXFUL MXSTM MY~ O9- OK1 P2P P2W Q2X R.K RHF RHI RNS ROL RPM SV3 TN5 TR2 WBKPD WH7 WIH WIK WIN WOHZO WXSBR WYJ YSK ZCA ZZTAW ~KM ACSMW CGR CUY CVF ECM EIF NPM AAYXX CITATION 7QG 7QL 7QP 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 K9. M7N P64 RC3 7X8 5PM |
ID | FETCH-LOGICAL-c5137-89bbc4e3db8af8e515f5f4f0aaf277a8e39ba4209fe7cf9eb16f7a6353686a193 |
IEDL.DBID | RPM |
ISSN | 0261-4189 |
IngestDate | Tue Sep 17 21:15:39 EDT 2024 Wed Dec 04 00:42:46 EST 2024 Tue Nov 19 05:43:12 EST 2024 Fri Dec 06 05:10:40 EST 2024 Sat Sep 28 08:35:29 EDT 2024 Sat Aug 24 01:04:05 EDT 2024 Thu Nov 14 02:20:49 EST 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 7 |
Keywords | Aspartyl protease Plasmepsin modeling Toxoplasma Plasmodium |
Language | English |
License | 2018 The Authors. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c5137-89bbc4e3db8af8e515f5f4f0aaf277a8e39ba4209fe7cf9eb16f7a6353686a193 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work |
ORCID | 0000-0001-5236-7056 0000-0003-1079-648X 0000-0002-1058-3620 0000-0003-4156-2109 |
OpenAccessLink | https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.201798047 |
PMID | 29519896 |
PQID | 2020927828 |
PQPubID | 35985 |
PageCount | 19 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_5881632 proquest_miscellaneous_2012918853 proquest_journals_2020927828 crossref_primary_10_15252_embj_201798047 pubmed_primary_29519896 wiley_primary_10_15252_embj_201798047_EMBJ201798047 springer_journals_10_15252_embj_201798047 |
PublicationCentury | 2000 |
PublicationDate | 03 April 2018 |
PublicationDateYYYYMMDD | 2018-04-03 |
PublicationDate_xml | – month: 04 year: 2018 text: 03 April 2018 day: 03 |
PublicationDecade | 2010 |
PublicationPlace | London |
PublicationPlace_xml | – name: London – name: England – name: Heidelberg – name: Hoboken |
PublicationTitle | The EMBO journal |
PublicationTitleAbbrev | EMBO J |
PublicationTitleAlternate | EMBO J |
PublicationYear | 2018 |
Publisher | Nature Publishing Group UK Blackwell Publishing Ltd John Wiley and Sons Inc |
Publisher_xml | – name: Nature Publishing Group UK – name: Blackwell Publishing Ltd – name: John Wiley and Sons Inc |
References | Silva, Lee, Gulnik, Maier, Collins, Bhat, Collins, Cachau, Luker, Gluzman, Francis, Oksman, Goldberg, Erickson (CR46) 1996; 93 Meyers, Goldberg (CR33) 2012; 12 Boddey, Hodder, Gunther, Gilson, Patsiouras, Kapp, Pearce, de Koning‐Ward, Simpson, Crabb, Cowman (CR8) 2010; 463 Ciana, Siegrist, Aissaoui, Marx, Racine, Meyer, Binkert, de Kanter, Fischli, Wittlin, Boss (CR10) 2013; 23 Dogga, Mukherjee, Jacot, Kockmann, Molino, Hammoudi, Hartkoorn, Hehl, Soldati‐Favre (CR15) 2017; 6 Hammoudi, Jacot, Mueller, Di Cristina, Dogga, Marq, Romano, Tosetti, Dubrot, Emre, Lunghi, Coppens, Yamamoto, Sojka, Pino, Soldati‐Favre (CR23) 2015; 11 Schmidt, Bergner, Schwede (CR41) 2014; 19 Hodder, Sleebs, Czabotar, Gazdik, Xu, O'Neill, Lopaticki, Nebl, Triglia, Smith, Lowes, Boddey, Cowman (CR24) 2015; 22 Reiss, Viebig, Brecht, Fourmaux, Soete, Di Cristina, Dubremetz, Soldati (CR40) 2001; 152 Huizing, Mondal, Hirsch (CR26) 2015; 58 Bedi, Patel, Mishra, Xiao, Yada, Bhaumik (CR5) 2016; 6 Daily (CR14) 2017; 19 Halgren, Murphy, Friesner, Beard, Frye, Pollard, Banks (CR21) 2004; 47 Madhavi Sastry, Adzhigirey, Day, Annabhimoju, Sherman (CR29) 2013; 27 Andrews, Fairlie, Madala, Ray, Wyatt, Hilton, Melville, Beattie, Gardiner, Reid, Stoermer, Skinner‐Adams, Berry, McCarthy (CR2) 2006; 50 McDonald, Shirley (CR30) 2009; 136 Coombs, Goldberg, Klemba, Berry, Kay, Mottram (CR13) 2001; 17 Goodswen, Kennedy, Ellis (CR20) 2013; 13 Shea, Jakle, Liu, Berry, Joiner, Soldati‐Favre (CR44) 2007; 8 Meissner, Reiss, Viebig, Carruthers, Toursel, Tomavo, Ajioka, Soldati (CR31) 2002; 115 Pino, Caldelari, Mukherjee, Vahokoski, Klages, Maco, Collins, Blackman, Kursula, Heussler, Brochet, Soldati‐Favre (CR37) 2017; 358 Tubert‐Brohman, Sherman, Repasky, Beuming (CR48) 2013; 53 Andreeva, Rumsh (CR1) 2001; 10 Montoya, Liesenfeld (CR34) 2004; 363 Seeliger, Nagar, Frank, Cao, Henderson, Kuriyan (CR43) 2007; 15 Coleman, Gubbels (CR12) 2012; 60 Nasamu, Glushakova, Russo, Vaupel, Oksman, Kim, Fremont, Tolia, Beck, Meyers, Niles, Zimmerberg, Goldberg (CR36) 2017; 358 Bhaumik, Horimoto, Xiao, Miura, Hidaka, Kiso, Wlodawer, Yada, Gustchina (CR7) 2011; 175 Asojo, Gulnik, Afonina, Yu, Ellman, Haque, Silva (CR3) 2003; 327 Benkert, Biasini, Schwede (CR6) 2011; 27 Gambini, Rizzi, Pedretti, Taglialatela‐Scafati, Carucci, Pancotti, Galli, Read, Giurisato, Romeo, Russo (CR19) 2015; 10 Farrell, Coleman, Benenati, Brown, Blader, Marth, Gubbels (CR18) 2014; 15 Karubiu, Bhakat, McGillewie, Soliman (CR28) 2015; 11 Halgren (CR22) 2009; 49 Soldati, Boothroyd (CR47) 1993; 260 Seeber, Steinfelder (CR42) 2016; 5 Hornak, Okur, Rizzo, Simmerling (CR25) 2006; 103 Plattner, Soldati‐Favre (CR38) 2008; 62 Bradley, Boothroyd (CR9) 1999; 100 Banerjee, Francis, Goldberg (CR4) 2003; 129 Muller, Hemphill (CR35) 2013; 43 Jaudzems, Tars, Maurops, Ivdra, Otikovs, Leitans, Kanepe‐Lapsa, Domraceva, Mutule, Trapencieris, Blackman, Jirgensons (CR27) 2014; 5 Buchs, Kim, Pouliquen, Sachs, Geisse, Mahnke, Hunt (CR100) 2009; 498 Dunn (CR17) 2002; 102 Meissner, Schluter, Soldati (CR32) 2002; 298 Coffey, Sleebs, Uboldi, Garnham, Franco, Marino, Panas, Ferguson, Enciso, O'Neill, Lopaticki, Stewart, Dewson, Smyth, Smith, Masters, Boothroyd, Boddey, Tonkin (CR11) 2015; 4 Donald, Carter, Ullman, Roos (CR16) 1996; 271 Shen, Zhang, Zhang, Zhou, Wang, Chen, Wang, Hodgkins, Iyer, Huang, Skarnes (CR45) 2014; 11 Recacha, Leitans, Akopjana, Aprupe, Trapencieris, Jaudzems, Jirgensons, Tars (CR39) 2015; 71 Turetzky, Chu, Hajagos, Bradley (CR49) 2010; 40 2012; 60 2017; 6 2004; 363 2015; 58 2006; 50 2015; 4 2013; 27 2015; 71 2013; 43 2013; 23 2004; 47 2015; 11 2015; 10 1993; 260 2010; 463 1996; 93 2009; 498 1999; 100 2012; 12 2009; 49 2009; 136 2017; 358 2010; 40 2002a; 115 2007; 15 2011; 175 2016; 5 2016; 6 2014; 5 2003; 327 2003; 129 2001; 152 2013; 13 2002; 102 2002b; 298 2015; 22 2013; 53 2007; 8 1996; 271 2014; 15 2017; 19 2014; 19 2001; 17 2011; 27 2008; 62 2014; 11 2006; 103 2001; 10 e_1_2_8_28_1 e_1_2_8_24_1 e_1_2_8_47_1 e_1_2_8_26_1 e_1_2_8_49_1 e_1_2_8_3_1 e_1_2_8_5_1 e_1_2_8_7_1 e_1_2_8_9_1 e_1_2_8_20_1 e_1_2_8_43_1 e_1_2_8_22_1 e_1_2_8_45_1 e_1_2_8_41_1 e_1_2_8_17_1 e_1_2_8_19_1 e_1_2_8_13_1 e_1_2_8_36_1 e_1_2_8_15_1 e_1_2_8_38_1 Coleman BI (e_1_2_8_14_1) 2012; 60 e_1_2_8_32_1 e_1_2_8_11_1 e_1_2_8_34_1 e_1_2_8_51_1 e_1_2_8_30_1 e_1_2_8_29_1 e_1_2_8_25_1 e_1_2_8_46_1 e_1_2_8_27_1 e_1_2_8_48_1 e_1_2_8_2_1 e_1_2_8_4_1 e_1_2_8_6_1 e_1_2_8_8_1 e_1_2_8_21_1 e_1_2_8_42_1 e_1_2_8_23_1 e_1_2_8_44_1 e_1_2_8_40_1 e_1_2_8_18_1 e_1_2_8_39_1 e_1_2_8_35_1 e_1_2_8_16_1 e_1_2_8_37_1 e_1_2_8_10_1 e_1_2_8_31_1 e_1_2_8_12_1 e_1_2_8_33_1 e_1_2_8_50_1 |
References_xml | – volume: 11 start-page: 1061 year: 2015 end-page: 1066 ident: CR28 article-title: Flap dynamics of plasmepsin proteases: insight into proposed parameters and molecular dynamics publication-title: Mol BioSyst contributor: fullname: Soliman – volume: 358 start-page: 518 year: 2017 end-page: 522 ident: CR36 article-title: Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion publication-title: Science contributor: fullname: Goldberg – volume: 327 start-page: 173 year: 2003 end-page: 181 ident: CR3 article-title: Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from publication-title: J Mol Biol contributor: fullname: Silva – volume: 175 start-page: 73 year: 2011 end-page: 84 ident: CR7 article-title: Crystal structures of the free and inhibited forms of plasmepsin I (PMI) from publication-title: J Struct Biol contributor: fullname: Gustchina – volume: 6 start-page: 31420 year: 2016 ident: CR5 article-title: Understanding the structural basis of substrate recognition by plasmepsin V to aid in the design of potent inhibitors publication-title: Sci Rep contributor: fullname: Bhaumik – volume: 4 start-page: e10809 year: 2015 ident: CR11 article-title: An aspartyl protease defines a novel pathway for export of proteins into the host cell publication-title: Elife contributor: fullname: Tonkin – volume: 50 start-page: 639 year: 2006 end-page: 648 ident: CR2 article-title: Potencies of human immunodeficiency virus protease inhibitors against and against murine malaria publication-title: Antimicrob Agents Chemother contributor: fullname: McCarthy – volume: 27 start-page: 221 year: 2013 end-page: 234 ident: CR29 article-title: Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments publication-title: J Comput Aided Mol Des contributor: fullname: Sherman – volume: 103 start-page: 915 year: 2006 end-page: 920 ident: CR25 article-title: HIV‐1 protease flaps spontaneously open and reclose in molecular dynamics simulations publication-title: Proc Natl Acad Sci USA contributor: fullname: Simmerling – volume: 47 start-page: 1750 year: 2004 end-page: 1759 ident: CR21 article-title: Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening publication-title: J Med Chem contributor: fullname: Banks – volume: 13 start-page: 133 year: 2013 end-page: 150 ident: CR20 article-title: A review of the infection, genetics, and evolution of : from the past to the present publication-title: Infect Genet Evol contributor: fullname: Ellis – volume: 71 start-page: 1531 year: 2015 end-page: 1539 ident: CR39 article-title: Structures of plasmepsin II from in complex with two hydroxyethylamine‐based inhibitors publication-title: Acta Crystallogr F Struct Biol Commun contributor: fullname: Tars – volume: 27 start-page: 343 year: 2011 end-page: 350 ident: CR6 article-title: Toward the estimation of the absolute quality of individual protein structure models publication-title: Bioinformatics contributor: fullname: Schwede – volume: 10 start-page: 2439 year: 2001 end-page: 2450 ident: CR1 article-title: Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin‐like enzymes publication-title: Protein Sci contributor: fullname: Rumsh – volume: 60 start-page: e3807 year: 2012 ident: CR12 article-title: A genetic screen to isolate host‐cell egress mutants publication-title: J Vis Exp contributor: fullname: Gubbels – volume: 129 start-page: 157 year: 2003 end-page: 165 ident: CR4 article-title: Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in publication-title: Mol Biochem Parasitol contributor: fullname: Goldberg – volume: 260 start-page: 349 year: 1993 end-page: 352 ident: CR47 article-title: Transient transfection and expression in the obligate intracellular parasite publication-title: Science contributor: fullname: Boothroyd – volume: 15 start-page: 299 year: 2007 end-page: 311 ident: CR43 article-title: c‐Src binds to the cancer drug imatinib with an inactive Abl/c‐Kit conformation and a distributed thermodynamic penalty publication-title: Structure contributor: fullname: Kuriyan – volume: 19 start-page: 28 year: 2017 ident: CR14 article-title: Malaria 2017: update on the clinical literature and management publication-title: Curr Infect Dis Rep contributor: fullname: Daily – volume: 40 start-page: 1037 year: 2010 end-page: 1044 ident: CR49 article-title: Processing and secretion of ROP13: a unique effector protein publication-title: Int J Parasitol contributor: fullname: Bradley – volume: 58 start-page: 5151 year: 2015 end-page: 5163 ident: CR26 article-title: Fighting malaria: structure‐guided discovery of nonpeptidomimetic plasmepsin inhibitors publication-title: J Med Chem contributor: fullname: Hirsch – volume: 62 start-page: 471 year: 2008 end-page: 487 ident: CR38 article-title: Hijacking of host cellular functions by the Apicomplexa publication-title: Annu Rev Microbiol contributor: fullname: Soldati‐Favre – volume: 12 start-page: 445 year: 2012 end-page: 455 ident: CR33 article-title: Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts publication-title: Curr Top Med Chem contributor: fullname: Goldberg – volume: 100 start-page: 103 year: 1999 end-page: 109 ident: CR9 article-title: Identification of the pro‐mature processing site of ROP1 by mass spectrometry publication-title: Mol Biochem Parasitol contributor: fullname: Boothroyd – volume: 11 start-page: e1005211 year: 2015 ident: CR23 article-title: Fundamental roles of the golgi‐associated aspartyl protease, ASP5, at the Host‐Parasite interface publication-title: PLoS Pathog contributor: fullname: Soldati‐Favre – volume: 19 start-page: 890 year: 2014 end-page: 897 ident: CR41 article-title: Modelling three‐dimensional protein structures for applications in drug design publication-title: Drug Discov Today contributor: fullname: Schwede – volume: 271 start-page: 14010 year: 1996 end-page: 14019 ident: CR16 article-title: Insertional tagging, cloning, and expression of the hypoxanthine‐xanthine‐guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation publication-title: J Biol Chem contributor: fullname: Roos – volume: 363 start-page: 1965 year: 2004 end-page: 1976 ident: CR34 article-title: Toxoplasmosis publication-title: Lancet contributor: fullname: Liesenfeld – volume: 152 start-page: 563 year: 2001 end-page: 578 ident: CR40 article-title: Identification and characterization of an escorter for two secretory adhesins in publication-title: J Cell Biol contributor: fullname: Soldati – volume: 10 start-page: e0142509 year: 2015 ident: CR19 article-title: Picomolar inhibition of plasmepsin V, an essential malaria protease, achieved exploiting the prime region publication-title: PLoS ONE contributor: fullname: Russo – volume: 22 start-page: 590 year: 2015 end-page: 596 ident: CR24 article-title: Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes publication-title: Nat Struct Mol Biol contributor: fullname: Cowman – volume: 358 start-page: 522 year: 2017 end-page: 528 ident: CR37 article-title: A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress publication-title: Science contributor: fullname: Soldati‐Favre – volume: 23 start-page: 658 year: 2013 end-page: 662 ident: CR10 article-title: Novel active anti‐malarials based on a hydroxy‐ethyl‐amine scaffold publication-title: Bioorg Med Chem Lett contributor: fullname: Boss – volume: 17 start-page: 532 year: 2001 end-page: 537 ident: CR13 article-title: Aspartic proteases of and other parasitic protozoa as drug targets publication-title: Trends Parasitol contributor: fullname: Mottram – volume: 136 start-page: 1477 year: 2009 end-page: 1489 ident: CR30 article-title: Past and future: vaccination against Eimeria publication-title: Parasitology contributor: fullname: Shirley – volume: 298 start-page: 837 year: 2002 end-page: 840 ident: CR32 article-title: Role of myosin A in powering parasite gliding and host cell invasion publication-title: Science contributor: fullname: Soldati – volume: 498 start-page: 199 year: 2009 end-page: 227 ident: CR100 article-title: High‐throughput insect cell protein expression applications publication-title: Methods Mol Biol contributor: fullname: Hunt – volume: 11 start-page: 399 year: 2014 end-page: 402 ident: CR45 article-title: Efficient genome modification by CRISPR‐Cas9 nickase with minimal off‐target effects publication-title: Nat Methods contributor: fullname: Skarnes – volume: 93 start-page: 10034 year: 1996 end-page: 10039 ident: CR46 article-title: Structure and inhibition of plasmepsin II, a hemoglobin‐degrading enzyme from publication-title: Proc Natl Acad Sci USA contributor: fullname: Erickson – volume: 15 start-page: 354 year: 2014 ident: CR18 article-title: Whole genome profiling of spontaneous and chemically induced mutations in publication-title: BMC Genom contributor: fullname: Gubbels – volume: 5 start-page: 1369 year: 2016 ident: CR42 article-title: Recent advances in understanding apicomplexan parasites publication-title: 1000Res contributor: fullname: Steinfelder – volume: 102 start-page: 4431 year: 2002 end-page: 4458 ident: CR17 article-title: Structure and mechanism of the pepsin‐like family of aspartic peptidases publication-title: Chem Rev contributor: fullname: Dunn – volume: 53 start-page: 1689 year: 2013 end-page: 1699 ident: CR48 article-title: Improved docking of polypeptides with glide publication-title: J Chem Inf Model contributor: fullname: Beuming – volume: 5 start-page: 373 year: 2014 end-page: 377 ident: CR27 article-title: Plasmepsin inhibitory activity and structure‐guided optimization of a potent hydroxyethylamine‐based antimalarial hit publication-title: ACS Med Chem Lett contributor: fullname: Jirgensons – volume: 8 start-page: 1018 year: 2007 end-page: 1034 ident: CR44 article-title: A family of aspartic proteases and a novel, dynamic and cell‐cycle‐dependent protease localization in the secretory pathway of publication-title: Traffic contributor: fullname: Soldati‐Favre – volume: 43 start-page: 115 year: 2013 end-page: 124 ident: CR35 article-title: culture systems for the study of apicomplexan parasites in farm animals publication-title: Int J Parasitol contributor: fullname: Hemphill – volume: 6 start-page: e27480 year: 2017 ident: CR15 article-title: A druggable secretory protein maturase of essential for invasion and egress publication-title: Elife contributor: fullname: Soldati‐Favre – volume: 115 start-page: 563 year: 2002 end-page: 574 ident: CR31 article-title: A family of transmembrane microneme proteins of contain EGF‐like domains and function as escorters publication-title: J Cell Sci contributor: fullname: Soldati – volume: 463 start-page: 627 year: 2010 end-page: 631 ident: CR8 article-title: An aspartyl protease directs malaria effector proteins to the host cell publication-title: Nature contributor: fullname: Cowman – volume: 49 start-page: 377 year: 2009 end-page: 389 ident: CR22 article-title: Identifying and characterizing binding sites and assessing druggability publication-title: J Chem Inf Model contributor: fullname: Halgren – volume: 363 start-page: 1965 year: 2004 end-page: 1976 article-title: Toxoplasmosis publication-title: Lancet – volume: 6 start-page: e27480 year: 2017 article-title: A druggable secretory protein maturase of essential for invasion and egress publication-title: Elife – volume: 11 start-page: 399 year: 2014 end-page: 402 article-title: Efficient genome modification by CRISPR‐Cas9 nickase with minimal off‐target effects publication-title: Nat Methods – volume: 27 start-page: 221 year: 2013 end-page: 234 article-title: Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments publication-title: J Comput Aided Mol Des – volume: 175 start-page: 73 year: 2011 end-page: 84 article-title: Crystal structures of the free and inhibited forms of plasmepsin I (PMI) from publication-title: J Struct Biol – volume: 23 start-page: 658 year: 2013 end-page: 662 article-title: Novel active anti‐malarials based on a hydroxy‐ethyl‐amine scaffold publication-title: Bioorg Med Chem Lett – volume: 102 start-page: 4431 year: 2002 end-page: 4458 article-title: Structure and mechanism of the pepsin‐like family of aspartic peptidases publication-title: Chem Rev – volume: 71 start-page: 1531 year: 2015 end-page: 1539 article-title: Structures of plasmepsin II from in complex with two hydroxyethylamine‐based inhibitors publication-title: Acta Crystallogr F Struct Biol Commun – volume: 4 start-page: e10809 year: 2015 article-title: An aspartyl protease defines a novel pathway for export of proteins into the host cell publication-title: Elife – volume: 115 start-page: 563 year: 2002a end-page: 574 article-title: A family of transmembrane microneme proteins of contain EGF‐like domains and function as escorters publication-title: J Cell Sci – volume: 100 start-page: 103 year: 1999 end-page: 109 article-title: Identification of the pro‐mature processing site of ROP1 by mass spectrometry publication-title: Mol Biochem Parasitol – volume: 327 start-page: 173 year: 2003 end-page: 181 article-title: Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from publication-title: J Mol Biol – volume: 12 start-page: 445 year: 2012 end-page: 455 article-title: Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts publication-title: Curr Top Med Chem – volume: 17 start-page: 532 year: 2001 end-page: 537 article-title: Aspartic proteases of and other parasitic protozoa as drug targets publication-title: Trends Parasitol – volume: 19 start-page: 28 year: 2017 article-title: Malaria 2017: update on the clinical literature and management publication-title: Curr Infect Dis Rep – volume: 47 start-page: 1750 year: 2004 end-page: 1759 article-title: Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening publication-title: J Med Chem – volume: 58 start-page: 5151 year: 2015 end-page: 5163 article-title: Fighting malaria: structure‐guided discovery of nonpeptidomimetic plasmepsin inhibitors publication-title: J Med Chem – volume: 463 start-page: 627 year: 2010 end-page: 631 article-title: An aspartyl protease directs malaria effector proteins to the host cell publication-title: Nature – volume: 5 start-page: 373 year: 2014 end-page: 377 article-title: Plasmepsin inhibitory activity and structure‐guided optimization of a potent hydroxyethylamine‐based antimalarial hit publication-title: ACS Med Chem Lett – volume: 27 start-page: 343 year: 2011 end-page: 350 article-title: Toward the estimation of the absolute quality of individual protein structure models publication-title: Bioinformatics – volume: 62 start-page: 471 year: 2008 end-page: 487 article-title: Hijacking of host cellular functions by the Apicomplexa publication-title: Annu Rev Microbiol – volume: 5 start-page: 1369 year: 2016 article-title: Recent advances in understanding apicomplexan parasites publication-title: 1000Res – volume: 271 start-page: 14010 year: 1996 end-page: 14019 article-title: Insertional tagging, cloning, and expression of the hypoxanthine‐xanthine‐guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation publication-title: J Biol Chem – volume: 498 start-page: 199 year: 2009 end-page: 227 article-title: High‐throughput insect cell protein expression applications publication-title: Methods Mol Biol – volume: 11 start-page: e1005211 year: 2015 article-title: Fundamental roles of the golgi‐associated aspartyl protease, ASP5, at the Host‐Parasite interface publication-title: PLoS Pathog – volume: 50 start-page: 639 year: 2006 end-page: 648 article-title: Potencies of human immunodeficiency virus protease inhibitors against and against murine malaria publication-title: Antimicrob Agents Chemother – volume: 19 start-page: 890 year: 2014 end-page: 897 article-title: Modelling three‐dimensional protein structures for applications in drug design publication-title: Drug Discov Today – volume: 10 start-page: 2439 year: 2001 end-page: 2450 article-title: Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin‐like enzymes publication-title: Protein Sci – volume: 43 start-page: 115 year: 2013 end-page: 124 article-title: culture systems for the study of apicomplexan parasites in farm animals publication-title: Int J Parasitol – volume: 22 start-page: 590 year: 2015 end-page: 596 article-title: Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes publication-title: Nat Struct Mol Biol – volume: 11 start-page: 1061 year: 2015 end-page: 1066 article-title: Flap dynamics of plasmepsin proteases: insight into proposed parameters and molecular dynamics publication-title: Mol BioSyst – volume: 136 start-page: 1477 year: 2009 end-page: 1489 article-title: Past and future: vaccination against Eimeria publication-title: Parasitology – volume: 8 start-page: 1018 year: 2007 end-page: 1034 article-title: A family of aspartic proteases and a novel, dynamic and cell‐cycle‐dependent protease localization in the secretory pathway of publication-title: Traffic – volume: 53 start-page: 1689 year: 2013 end-page: 1699 article-title: Improved docking of polypeptides with glide publication-title: J Chem Inf Model – volume: 152 start-page: 563 year: 2001 end-page: 578 article-title: Identification and characterization of an escorter for two secretory adhesins in publication-title: J Cell Biol – volume: 358 start-page: 518 year: 2017 end-page: 522 article-title: Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion publication-title: Science – volume: 260 start-page: 349 year: 1993 end-page: 352 article-title: Transient transfection and expression in the obligate intracellular parasite publication-title: Science – volume: 60 start-page: e3807 year: 2012 article-title: A genetic screen to isolate host‐cell egress mutants publication-title: J Vis Exp – volume: 93 start-page: 10034 year: 1996 end-page: 10039 article-title: Structure and inhibition of plasmepsin II, a hemoglobin‐degrading enzyme from publication-title: Proc Natl Acad Sci USA – volume: 103 start-page: 915 year: 2006 end-page: 920 article-title: HIV‐1 protease flaps spontaneously open and reclose in molecular dynamics simulations publication-title: Proc Natl Acad Sci USA – volume: 49 start-page: 377 year: 2009 end-page: 389 article-title: Identifying and characterizing binding sites and assessing druggability publication-title: J Chem Inf Model – volume: 40 start-page: 1037 year: 2010 end-page: 1044 article-title: Processing and secretion of ROP13: a unique effector protein publication-title: Int J Parasitol – volume: 15 start-page: 354 year: 2014 article-title: Whole genome profiling of spontaneous and chemically induced mutations in publication-title: BMC Genom – volume: 298 start-page: 837 year: 2002b end-page: 840 article-title: Role of myosin A in powering parasite gliding and host cell invasion publication-title: Science – volume: 15 start-page: 299 year: 2007 end-page: 311 article-title: c‐Src binds to the cancer drug imatinib with an inactive Abl/c‐Kit conformation and a distributed thermodynamic penalty publication-title: Structure – volume: 13 start-page: 133 year: 2013 end-page: 150 article-title: A review of the infection, genetics, and evolution of : from the past to the present publication-title: Infect Genet Evol – volume: 10 start-page: e0142509 year: 2015 article-title: Picomolar inhibition of plasmepsin V, an essential malaria protease, achieved exploiting the prime region publication-title: PLoS ONE – volume: 129 start-page: 157 year: 2003 end-page: 165 article-title: Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in publication-title: Mol Biochem Parasitol – volume: 6 start-page: 31420 year: 2016 article-title: Understanding the structural basis of substrate recognition by plasmepsin V to aid in the design of potent inhibitors publication-title: Sci Rep – volume: 358 start-page: 522 year: 2017 end-page: 528 article-title: A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress publication-title: Science – ident: e_1_2_8_21_1 doi: 10.1371/journal.pone.0142509 – ident: e_1_2_8_13_1 doi: 10.7554/eLife.10809 – volume: 60 start-page: e3807 year: 2012 ident: e_1_2_8_14_1 article-title: A genetic screen to isolate Toxoplasma gondii host‐cell egress mutants publication-title: J Vis Exp contributor: fullname: Coleman BI – ident: e_1_2_8_8_1 doi: 10.1016/j.jsb.2011.04.009 – ident: e_1_2_8_7_1 doi: 10.1093/bioinformatics/btq662 – ident: e_1_2_8_25_1 doi: 10.1371/journal.ppat.1005211 – ident: e_1_2_8_28_1 doi: 10.1021/jm5014133 – ident: e_1_2_8_49_1 doi: 10.1126/science.8469986 – ident: e_1_2_8_6_1 doi: 10.1038/srep31420 – ident: e_1_2_8_43_1 doi: 10.1016/j.drudis.2013.10.027 – ident: e_1_2_8_26_1 doi: 10.1038/nsmb.3061 – ident: e_1_2_8_50_1 doi: 10.1021/ci400128m – ident: e_1_2_8_27_1 doi: 10.1073/pnas.0508452103 – ident: e_1_2_8_10_1 doi: 10.1016/S0166-6851(99)00035-3 – ident: e_1_2_8_29_1 doi: 10.1021/ml4004952 – ident: e_1_2_8_35_1 doi: 10.2174/156802612799362959 – ident: e_1_2_8_40_1 doi: 10.1146/annurev.micro.62.081307.162802 – ident: e_1_2_8_51_1 doi: 10.1016/j.ijpara.2010.02.014 – ident: e_1_2_8_24_1 doi: 10.1021/ci800324m – ident: e_1_2_8_11_1 doi: 10.1007/978-1-59745-196-3_14 – ident: e_1_2_8_33_1 doi: 10.1242/jcs.115.3.563 – ident: e_1_2_8_45_1 doi: 10.1016/j.str.2007.01.015 – ident: e_1_2_8_20_1 doi: 10.1186/1471-2164-15-354 – ident: e_1_2_8_34_1 doi: 10.1126/science.1074553 – ident: e_1_2_8_17_1 doi: 10.7554/eLife.27480 – ident: e_1_2_8_5_1 doi: 10.1016/S0166-6851(03)00119-1 – ident: e_1_2_8_39_1 doi: 10.1126/science.aaf8675 – ident: e_1_2_8_44_1 doi: 10.12688/f1000research.7924.1 – ident: e_1_2_8_48_1 doi: 10.1073/pnas.93.19.10034 – ident: e_1_2_8_37_1 doi: 10.1016/j.ijpara.2012.08.004 – ident: e_1_2_8_47_1 doi: 10.1038/nmeth.2857 – ident: e_1_2_8_38_1 doi: 10.1126/science.aan1478 – ident: e_1_2_8_23_1 doi: 10.1021/jm030644s – ident: e_1_2_8_9_1 doi: 10.1038/nature08728 – ident: e_1_2_8_2_1 doi: 10.1110/ps.25801 – ident: e_1_2_8_36_1 doi: 10.1016/S0140-6736(04)16412-X – ident: e_1_2_8_12_1 doi: 10.1016/j.bmcl.2012.11.118 – ident: e_1_2_8_18_1 doi: 10.1074/jbc.271.24.14010 – ident: e_1_2_8_42_1 doi: 10.1083/jcb.152.3.563 – ident: e_1_2_8_15_1 doi: 10.1016/S1471-4922(01)02037-2 – ident: e_1_2_8_4_1 doi: 10.1016/S0022-2836(03)00036-6 – ident: e_1_2_8_19_1 doi: 10.1021/cr010167q – ident: e_1_2_8_32_1 doi: 10.1017/S0031182009006349 – ident: e_1_2_8_22_1 doi: 10.1016/j.meegid.2012.08.012 – ident: e_1_2_8_30_1 doi: 10.1039/C4MB00631C – ident: e_1_2_8_3_1 doi: 10.1128/AAC.50.2.639-648.2006 – ident: e_1_2_8_41_1 doi: 10.1107/S2053230X15022049 – ident: e_1_2_8_16_1 doi: 10.1007/s11908-017-0583-8 – ident: e_1_2_8_46_1 doi: 10.1111/j.1600-0854.2007.00589.x – ident: e_1_2_8_31_1 doi: 10.1007/s10822-013-9644-8 |
SSID | ssj0005871 |
Score | 2.3772664 |
Snippet | Toxoplasma gondii
aspartyl protease 3 (TgASP3) phylogenetically clusters with
Plasmodium falciparum
Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are... Toxoplasma gondii aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are... aspartyl protease 3 (TgASP3) phylogenetically clusters with Plasmepsins IX and X (PfPMIX, PfPMX). These proteases are essential for parasite survival, acting... Toxoplasma gondii aspartyl protease 3 (Tg ASP 3) phylogenetically clusters with Plasmodium falciparum Plasmepsins IX and X (Pf PMIX , Pf PMX ). These proteases... |
SourceID | pubmedcentral proquest crossref pubmed wiley springer |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
SubjectTerms | Antimalarials - chemistry Antimalarials - pharmacology Aspartic Acid Endopeptidases - chemistry Aspartic Acid Endopeptidases - metabolism Aspartic Acid Proteases - antagonists & inhibitors Aspartic Acid Proteases - metabolism Aspartic endopeptidase Aspartyl protease Catalysis Cysteine Determinants Dose-Response Relationship, Drug Drug Resistance - drug effects Drug Resistance - physiology Egress EMBO23 EMBO31 EMBO40 Homology Inhibitors Inhibitory Concentration 50 modeling Models, Molecular Molecular docking Molecular Docking Simulation Mutation Parasite resistance Parasites Parasitic Sensitivity Tests Phenylalanine Phenylalanine - drug effects Phenylalanine - genetics Phylogeny Plasmepsin Plasmodium Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Protease Protease Inhibitors - pharmacology Proteases Proteins Protozoan Proteins - chemistry Protozoan Proteins - genetics Recognition Recombinant Proteins - genetics Residues Selectivity Sensitivity Sequence Alignment Substrates Toxoplasma Toxoplasma - drug effects Toxoplasma - genetics Toxoplasma gondii Tyrosine |
SummonAdditionalLinks | – databaseName: Springer Nature OA Free Journals dbid: C6C link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3BbtQwEB1BEYILggIlUJCROMAhIrGdxHOEVauqUjlRqbfITmyxaJtdNanUqj_PjDebsioIcUtkJ7E9Y8-beDwP4AOGgGXhdepRZ6nOtUuda12KSntsm4ZANh8UPvlWHp3q47PibEySxGdhft-_L2QhP_tz95MjsCo0ma7uwwMywBWr8qyc3cZymOhZxZ8pOjc45vD5wwu2zc8dTHk3NHLaH91Gr9H8HD6FJyNuFF_Wgn4G93y3Cw_XTJLXu_BotiFuew43zG_Gp8yF7VpB7jRDxG4QzJqy8L3wV6uFnXeCoJ_oIw1OJJAQy0APDPNzS84uaaXgaHMmXRIaGzHE8Npe2NU8RqHzsRhhaTm6GK4XImZ7IHvYv4DTw4Pvs6N05FhImyJXZKDQuUZ71Tpjg_E0uKEIOmTWBllV1niFzmqZYfBVE5BW9jJUllCKKk1pCf29hJ1u2flXIJzCXLWokWFJaDOUVNk3VoamDU62CXzcDH29WqfSqNkFYSnVLKV6klIC-xvR1OOc6qmUmiEJ0ZgE3k_FNLa8xWE7v7zkOoRfckMYJIG9tSSnb0kCk2iwTKDakvFUgTNtb5d08x8x43ZhDOFWmcCnjTbcNuuvXVBRXf7V1frg5OvxdPf6P77wBh7TtYlhRGofdoaLS_-WENLg3sXZ8QulHwxb priority: 102 providerName: Springer Nature |
Title | Modeling and resistant alleles explain the selectivity of antimalarial compound 49c towards apicomplexan aspartyl proteases |
URI | https://link.springer.com/article/10.15252/embj.201798047 https://onlinelibrary.wiley.com/doi/abs/10.15252%2Fembj.201798047 https://www.ncbi.nlm.nih.gov/pubmed/29519896 https://www.proquest.com/docview/2020927828 https://search.proquest.com/docview/2012918853 https://pubmed.ncbi.nlm.nih.gov/PMC5881632 |
Volume | 37 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fi9QwEB5uD0RfRM8fVz2XCD7oQ2-3adomj1ruOA5WfPDg3kqSJljZ7S63PfDwn3cm21aXQwQfS9I26Uw73zRf5gN4p7xXeeZE7JSYxyIRJjamNrFKhVO1tQiyaaPw4nN-cSUur7PrA8iGvTCBtG9Nc9ouV6dt8y1wKzcrOxt4YrMvizKTEmEEn01gguF3SNEHXocMWVb4sSISqfp6PhnP-MytzHeicxVKzgXp73EEGEpSxf4_o9I9qHmfMTkum-6D2hCVzp_A4x5Oso-7YT-FA9cewYOdwOTdETwsBz23Z_CTZM9o8znTbc0wyybk2HaMxFRwxsz92Cx10zJEhGwb1HGCrgRbezyha1Yac2B0VkYkdNJiYkJZ1gXW7ZbpTRPI6bRbhmn8St10d0sWikBgmNw-h6vzs6_lRdxLL8Q2S1KMW8oYK1xaG6m9dAh6fOaFn2vteVFo6VJltOBz5V1hvcIPfu4LjeAlzWWuERS-gMN23bpjYCZVSVoroQit-HquOHZ2VnNva294HcH74dFXm12FjYoyEzJYRQarRoNFcDKYpupftS224jA4Ah0ZwduxGZ8trXzo1q1vqQ_CmkQiNIng5c6S470GF4ig2LPx2IEKcO-3oF-GQty9H0bwYfCG38P66xTS4C7_mmp1tvh0OR69-u-xvYZHeBUZuEbpCRx2N7fuDcKozkxhUubllEJZNg2v0C9aQB6g |
link.rule.ids | 230,314,727,780,784,885,27924,27925,41120,42189,51576,53791,53793 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwEB2VIlQuqJSvQAtG4gCHdBPbSewjXbVaSrfi0Eq9RbZji6Dd7KqbSlT8ecbeJHRVISSOkZ3E9ozjN_HzPIAP0jmZZ5bHVvIk5inXsdaVjiXjVlbGIMj2B4Wn5_nkkp9eZVdbkPVnYQJp3-j6sJnND5v6e-BWLudm1PPERt-m40wIhBF09AAeZqyQaR-k98wOEeKs8GuFp0J2GX0ymtGRnesfntBVSJFwr8BHEWJI4XP2312X7oHN-5zJYeN0E9aGdelkF550gJJ8Xjf8KWzZZg8erSUmb_dgZ9wruj2DX174zB8_J6qpCMbZHjs2LfFyKthnYn8uZ6puCGJCsgr6OEFZgiwc3tDWc4VRMLor8TR0r8ZEuDSkDbzbFVHLOtDT_XkZovA7dd3ezkhIA4EL5eo5XJ4cX4wncSe-EJssZbhySa0Nt6zSQjlhEfa4zHGXKOVoUShhmdSK00Q6Wxgn8ZOfu0IhfGG5yBXCwhew3Swa-wqIZjJlleTS4xVXJZJiZWsUdaZymlYRfOyHvlyuc2yUPjbxBiu9wcrBYBHs96Ypu8m2wlJsBkWoIyJ4PxTj2Pq9D9XYxY2vg8AmFQhOIni5tuTwrt4FIig2bDxU8Cm4N0vQM0Mq7s4TI_jUe8OfZv21Cyy4y7-6Wh5Pj06Hq9f_3bZ3sDO5mJ6VZ1_Ov76Bx_hEEZhHbB-22-sbe4CgqtVvwxT6DRJbIDI |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwEB1BER8XBOUrUMBIHOCQJrGdxD7C0lUpbNUDlXqLbMcWi3azUTeVqPjzjL1J6KpCSBwjO4ntGcdv4ud5AG-lc7LILY-t5GnMM65jrWsdS8atrI1BkO0PCs-Oi8NTfnSWn12R-gqkfaPn-81iud_MvwduZbs0ycATS05mk1wIhBE0aWuX3IRbOUMnGwL1gd0hQqwVfq_wTMg-q09Oc5rYpf7hSV2lFCn3KnwUYYYUPm__1bXpGuC8zpscN0-3oW1Ym6YP4H4PKsmHTeMfwg3b7MLtjczk5S7cnQyqbo_glxc_80fQiWpqgrG2x49NR7ykCvab2J_tQs0bgriQrINGTlCXICuHN3TzpcJIGF2WeCq6V2QiXBrSBe7tmqh2Hijq_swMUfitOu8uFySkgsDFcv0YTqcH3yaHcS_AEJs8Y7h6Sa0Nt6zWQjlhEfq43HGXKuVoWSphmdSK01Q6Wxon8bNfuFIhhGGFKBRCwyew06wa-wyIZjJjteTSYxZXp5JiZWsUdaZ2mtYRvBuGvmo3eTYqH594g1XeYNVosAj2BtNU_YRbYyk2gyLcERG8GYtxbP3-h2rs6sLXQXCTCQQoETzdWHJ81-ACEZRbNh4r-DTc2yXonSEdd--NEbwfvOFPs_7aBRbc5V9drQ5mH4_Gq-f_3bbXcOfk07T6-vn4ywu4hw8UgXzE9mCnO7-wLxFXdfpVmEG_AS4HIUU |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Modeling+and+resistant+alleles+explain+the+selectivity+of+antimalarial+compound+49c+towards+apicomplexan+aspartyl+proteases&rft.jtitle=The+EMBO+journal&rft.au=Mukherjee%2C+Budhaditya&rft.au=Tessaro%2C+Francesca&rft.au=Vahokoski%2C+Juha&rft.au=Kursula%2C+Inari&rft.date=2018-04-03&rft.pub=John+Wiley+and+Sons+Inc&rft.issn=0261-4189&rft.eissn=1460-2075&rft.volume=37&rft.issue=7&rft_id=info:doi/10.15252%2Fembj.201798047&rft_id=info%3Apmid%2F29519896&rft.externalDBID=PMC5881632 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0261-4189&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0261-4189&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0261-4189&client=summon |