Naturally Occurring A51V Variant of Human Cytochrome c Destabilizes the Native State and Enhances Peroxidase Activity
The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation d...
Saved in:
| Published in | The journal of physical chemistry. B Vol. 123; no. 42; pp. 8939 - 8953 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
24.10.2019
|
| Online Access | Get full text |
Cover
Loading…
| Abstract | The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH1/2, of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high-spin heme transient. The pH1/2 for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the k cat values for its peroxidase activity increase by 6- to 15-fold in the pH range of 5–8 versus those of the WT protein. These data along with previously reported data for the other THC4-linked variants, G41S and Y48H, underscore the role of Ω-loop C (residues 40–57) in modulating the peroxidase activity of cytochrome c early in apoptosis. |
|---|---|
| AbstractList | The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH1/2, of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high-spin heme transient. The pH1/2 for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the k cat values for its peroxidase activity increase by 6- to 15-fold in the pH range of 5–8 versus those of the WT protein. These data along with previously reported data for the other THC4-linked variants, G41S and Y48H, underscore the role of Ω-loop C (residues 40–57) in modulating the peroxidase activity of cytochrome c early in apoptosis. The A51V variant of human cytochrome is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH , of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high-spin heme transient. The pH for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the values for its peroxidase activity increase by 6- to 15-fold in the pH range of 5-8 versus those of the WT protein. These data along with previously reported data for the other THC4-linked variants, G41S and Y48H, underscore the role of Ω-loop C (residues 40-57) in modulating the peroxidase activity of cytochrome early in apoptosis. The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the A51V variant shows only minor changes in tertiary structure relative to the wild type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH 1/2 , of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high spin heme transient. The pH 1/2 for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the k cat values for its peroxidase activity increase by 6 to 15 fold in the pH range 5 to 8 versus those of the WT protein. These data along with previously reported data for the other THC4–linked variants, G41S and Y48H, underscore the role of Ω-loop C (residues 40 – 57) in modulating the peroxidase activity of cytochrome c early in apoptosis. |
| Author | Lei, Haotian Bowler, Bruce E |
| AuthorAffiliation | Department of Chemistry and Biochemistry, Center for Bimolecular Structure and Dynamics |
| AuthorAffiliation_xml | – name: Department of Chemistry and Biochemistry, Center for Bimolecular Structure and Dynamics |
| Author_xml | – sequence: 1 givenname: Haotian surname: Lei fullname: Lei, Haotian – sequence: 2 givenname: Bruce E orcidid: 0000-0003-1543-2466 surname: Bowler fullname: Bowler, Bruce E email: bruce.bowler@umontana.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31557440$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kc1vEzEQxS1URD_gzgn5yIEEf6_3ghSlhSJVFAno1fJ6ZxtXu3awvRXhr8cloYIDB8uW5vfezPidoqMQAyD0kpIlJYy-tS4v77auW7YdkVq1T9AJlYws6mmODm9FiTpGpznfEcIk0-oZOuZUykYIcoLmT7bMyY7jDl87N6fkwy1eSXqDb2zyNhQcB3w5Tzbg9a5Et0lxAuzwOeRiOz_6n5Bx2QCuPv4e8JdiC2AbenwRNja4Wv0MKf7wvc2AV65Cvuyeo6eDHTO8ONxn6Nv7i6_ry8XV9YeP69XVwgrOy4JKYgfWUqWgHXreOyGFZsxp3goHkhPthGgABkKE5FZ1ve0HJrpe6E5TBfwMvdv7budugt5BKHVXs01-smlnovXm30rwG3Mb743SlGsmq8Hrg0GK3-e6s5l8djCONkCcs2GsbanQjWoqSvaoSzHnBMNjG0rMQ1qmpmUe0jKHtKrk1d_jPQr-xFOBN3vgtzTOKdTf-r_fLwDNpNU |
| CitedBy_id | crossref_primary_10_1016_j_bbadis_2024_167134 crossref_primary_10_31857_S0320972521010061 crossref_primary_10_1021_jacs_2c08325 crossref_primary_10_1042_BCJ20200793 crossref_primary_10_2139_ssrn_3935490 crossref_primary_10_3390_sym14040767 crossref_primary_10_1016_j_jinorgbio_2022_111819 crossref_primary_10_1039_D3ME00196B crossref_primary_10_1016_j_jmb_2021_167057 crossref_primary_10_1021_acsomega_3c00220 crossref_primary_10_1039_D0RA09961A crossref_primary_10_1021_acsomega_2c01256 crossref_primary_10_1134_S0006297921010065 crossref_primary_10_1016_j_abb_2021_108980 crossref_primary_10_1016_j_abb_2021_109112 crossref_primary_10_1016_j_bbapap_2023_140897 crossref_primary_10_1038_s41418_024_01284_8 crossref_primary_10_1016_j_jinorgbio_2019_110924 crossref_primary_10_1021_acs_inorgchem_1c02322 crossref_primary_10_1016_j_bioelechem_2021_107956 crossref_primary_10_1021_acsomega_0c05746 crossref_primary_10_3389_fgene_2021_783455 crossref_primary_10_1016_j_jinorgbio_2023_112296 |
| Cites_doi | 10.1021/acs.chemrev.7b00257 10.1016/S0065-3233(08)60336-8 10.1038/nchembio727 10.1016/j.ccr.2010.09.014 10.1016/S0022-2836(03)00698-3 10.1007/s11022-004-8228-3 10.1021/bi048141r 10.1038/1810 10.1016/S0021-9258(18)32288-9 10.1042/BJ20130758 10.1016/j.jinorgbio.2018.02.022 10.1080/09537104.2018.1543866 10.1016/S0021-9258(19)86087-8 10.1002/prot.20757 10.1021/ja405725f 10.1107/S0907444909052925 10.1021/ja01852a006 10.1021/bi0524971 10.1021/bi961915m 10.1021/bi972188d 10.1021/bi0515873 10.1007/978-3-642-74536-2 10.1126/science.7618079 10.1107/S0907444912048524 10.1016/S0021-9258(18)63167-9 10.1021/bi301599g 10.3324/haematol.2016.146316 10.1007/s00726-018-2574-y 10.1021/acs.jpclett.7b00597 10.1021/cr400415k 10.1016/j.jinorgbio.2015.12.025 10.1021/bi00694a018 10.1042/BJ20131386 10.1021/ja01111a052 10.1111/bjh.14421 10.1107/S0907444913000061 10.1021/bi981698k 10.1021/ja971756+ 10.1042/bj2580599 10.1016/0005-2795(81)90217-8 10.1042/bj2580595 10.1021/acs.biochem.7b00890 10.1016/0005-2728(76)90081-5 10.1016/S0021-9258(17)34308-9 10.1046/j.1432-1327.2001.02335.x 10.1016/S0021-9258(19)42776-2 10.1016/S0021-9258(18)34916-0 10.1042/bj2460043 10.1107/S0907444909042073 10.1021/acs.biochem.8b00520 10.1002/bip.22164 10.1021/ja106328k 10.1073/pnas.1323828111 10.1021/bi701237b 10.1107/S2059798317016035 10.1021/bi048218b 10.1042/bj0710570 10.1021/bi700992y 10.1038/ng.103 10.1038/srep30447 10.1021/bi00421a014 10.1016/S0006-3495(98)74000-7 10.1021/acs.biochem.9b00295 10.1007/s00775-018-1603-3 10.1107/S0907444909042589 10.1021/acs.jpcb.6b01497 10.1039/c1ob05552f 10.1107/S0907444911001314 10.1146/annurev.biochem.73.011303.073706 10.1007/s00775-014-1174-x 10.1021/bi000266i 10.1101/gad.272278.115 10.1016/j.bbadis.2013.12.002 10.1021/ja9717572 10.1021/bi00434a012 10.1016/S0092-8674(00)80085-9 10.1016/j.jmb.2006.04.035 10.1038/nature06407 10.1021/bi034958t 10.1016/0003-2697(72)90451-4 10.1021/jp963142h 10.1016/S0022-2836(03)00697-1 10.1021/acs.accounts.5b00106 10.1038/nature06522 10.1107/S0907444910007493 10.1016/j.jmb.2004.08.005 10.1007/s00775-012-0973-1 10.1021/jacs.6b10745 10.1021/bi016060e 10.1021/acs.biochem.7b00342 10.1016/j.bbrc.2004.11.105 10.1016/j.bbrc.2003.10.182 |
| ContentType | Journal Article |
| DBID | NPM AAYXX CITATION 7X8 5PM |
| DOI | 10.1021/acs.jpcb.9b05869 |
| DatabaseName | PubMed CrossRef MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | PubMed CrossRef MEDLINE - Academic |
| DatabaseTitleList | PubMed |
| 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 |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry |
| EISSN | 1520-5207 |
| EndPage | 8953 |
| ExternalDocumentID | 10_1021_acs_jpcb_9b05869 31557440 a37183935 |
| Genre | Research Support, U.S. Gov't, Non-P.H.S Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIGMS NIH HHS grantid: P20 GM103546 – fundername: NIGMS NIH HHS grantid: P41 GM103393 |
| GroupedDBID | - .K2 02 123 29L 53G 55A 5VS 7~N 85S 8RP AABXI ABFLS ABMVS ABPTK ABUCX ACGFS ACNCT ACS AEESW AENEX AFEFF ALMA_UNASSIGNED_HOLDINGS AQSVZ BAANH CS3 DU5 EBS ED ED~ EJD F20 F5P GNL IH9 IHE JG JG~ K2 PZZ RNS ROL TAE TN5 UI2 UKR UPT VF5 VG9 VQA W1F WH7 X YZZ ZGI ZHY --- -~X .DC 4.4 AAHBH ABJNI ABQRX ACBEA ADHLV AHGAQ CUPRZ GGK NPM XSW YQT ~02 AAYXX CITATION 7X8 5PM |
| ID | FETCH-LOGICAL-a433t-150af29166e9fd3dc454822c8394ce5308c447eef00453a6bdadf24bd48b816e3 |
| IEDL.DBID | ACS |
| ISSN | 1520-6106 |
| IngestDate | Tue Sep 17 21:12:55 EDT 2024 Fri Aug 16 10:02:06 EDT 2024 Fri Aug 23 01:05:53 EDT 2024 Sat Sep 28 08:28:05 EDT 2024 Thu Aug 27 13:43:59 EDT 2020 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 42 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-a433t-150af29166e9fd3dc454822c8394ce5308c447eef00453a6bdadf24bd48b816e3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0003-1543-2466 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813825 |
| PMID | 31557440 |
| PQID | 2299148767 |
| PQPubID | 23479 |
| PageCount | 15 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_6813825 proquest_miscellaneous_2299148767 crossref_primary_10_1021_acs_jpcb_9b05869 pubmed_primary_31557440 acs_journals_10_1021_acs_jpcb_9b05869 |
| ProviderPackageCode | JG~ 55A AABXI GNL VF5 7~N VG9 W1F ACS AEESW AFEFF .K2 ABMVS ABUCX IH9 BAANH AQSVZ ED~ UI2 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-10-24 |
| PublicationDateYYYYMMDD | 2019-10-24 |
| PublicationDate_xml | – month: 10 year: 2019 text: 2019-10-24 day: 24 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The journal of physical chemistry. B |
| PublicationTitleAlternate | J. Phys. Chem. B |
| PublicationYear | 2019 |
| Publisher | American Chemical Society |
| Publisher_xml | – name: American Chemical Society |
| References | ref9/cit9 ref45/cit45 Hütteman M. (ref2/cit2) 2014 ref3/cit3 ref27/cit27 ref63/cit63 ref16/cit16 ref92/cit92 ref52/cit52 ref23/cit23 ref31/cit31 ref85/cit85 ref77/cit77 Dickerson R. E. (ref1/cit1) 1975; 11 ref34/cit34 Noble R. W. (ref50/cit50) 1970; 245 ref71/cit71 ref37/cit37 Wilson M. T. (ref56/cit56) 1996 ref20/cit20 ref48/cit48 Davis L. A. (ref81/cit81) 1974; 249 ref60/cit60 ref74/cit74 ref17/cit17 ref82/cit82 ref10/cit10 ref35/cit35 ref53/cit53 ref19/cit19 ref93/cit93 ref21/cit21 ref42/cit42 ref46/cit46 Moore G. R. (ref8/cit8) 1990 ref49/cit49 ref13/cit13 ref61/cit61 ref75/cit75 ref67/cit67 ref24/cit24 Robinson J. B. (ref88/cit88) 1983; 258 ref90/cit90 Osheroff N. (ref59/cit59) 1980; 255 ref64/cit64 ref78/cit78 ref54/cit54 ref6/cit6 ref36/cit36 ref18/cit18 ref83/cit83 ref65/cit65 ref79/cit79 Dyson H. J. (ref38/cit38) 1982; 257 ref11/cit11 ref25/cit25 ref29/cit29 ref72/cit72 ref76/cit76 ref86/cit86 ref32/cit32 ref39/cit39 ref14/cit14 ref57/cit57 ref5/cit5 ref51/cit51 ref43/cit43 ref80/cit80 ref28/cit28 ref40/cit40 ref68/cit68 ref94/cit94 Drew H. R. (ref89/cit89) 1978; 253 ref91/cit91 ref26/cit26 ref55/cit55 ref73/cit73 ref69/cit69 ref12/cit12 ref15/cit15 ref62/cit62 ref66/cit66 ref41/cit41 ref58/cit58 ref95/cit95 ref22/cit22 ref33/cit33 ref87/cit87 ref4/cit4 ref30/cit30 ref47/cit47 ref84/cit84 ref44/cit44 ref70/cit70 ref7/cit7 |
| References_xml | – ident: ref17/cit17 doi: 10.1021/acs.chemrev.7b00257 – ident: ref75/cit75 doi: 10.1016/S0065-3233(08)60336-8 – ident: ref5/cit5 doi: 10.1038/nchembio727 – ident: ref55/cit55 doi: 10.1016/j.ccr.2010.09.014 – ident: ref82/cit82 doi: 10.1016/S0022-2836(03)00698-3 – ident: ref91/cit91 doi: 10.1007/s11022-004-8228-3 – ident: ref33/cit33 doi: 10.1021/bi048141r – ident: ref69/cit69 doi: 10.1038/1810 – volume: 258 start-page: 6772 year: 1983 ident: ref88/cit88 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)32288-9 contributor: fullname: Robinson J. B. – ident: ref18/cit18 doi: 10.1042/BJ20130758 – ident: ref40/cit40 doi: 10.1016/j.jinorgbio.2018.02.022 – ident: ref14/cit14 doi: 10.1080/09537104.2018.1543866 – volume: 255 start-page: 1689 year: 1980 ident: ref59/cit59 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)86087-8 contributor: fullname: Osheroff N. – ident: ref58/cit58 doi: 10.1002/prot.20757 – ident: ref71/cit71 doi: 10.1021/ja405725f – ident: ref47/cit47 doi: 10.1107/S0907444909052925 – ident: ref57/cit57 doi: 10.1021/ja01852a006 – ident: ref90/cit90 doi: 10.1021/bi0524971 – ident: ref74/cit74 doi: 10.1021/bi961915m – ident: ref28/cit28 doi: 10.1021/bi972188d – ident: ref35/cit35 doi: 10.1021/bi0515873 – volume-title: Cytochromes c: Evolutionary, Structural and Physicochemical Aspects year: 1990 ident: ref8/cit8 doi: 10.1007/978-3-642-74536-2 contributor: fullname: Moore G. R. – ident: ref67/cit67 doi: 10.1126/science.7618079 – ident: ref41/cit41 doi: 10.1107/S0907444912048524 – volume: 245 start-page: 2409 year: 1970 ident: ref50/cit50 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)63167-9 contributor: fullname: Noble R. W. – ident: ref30/cit30 doi: 10.1021/bi301599g – volume: 11 start-page: 397 volume-title: The Enzymes year: 1975 ident: ref1/cit1 contributor: fullname: Dickerson R. E. – ident: ref16/cit16 doi: 10.3324/haematol.2016.146316 – ident: ref54/cit54 doi: 10.1007/s00726-018-2574-y – ident: ref92/cit92 doi: 10.1021/acs.jpclett.7b00597 – ident: ref9/cit9 doi: 10.1021/cr400415k – ident: ref29/cit29 doi: 10.1016/j.jinorgbio.2015.12.025 – ident: ref65/cit65 doi: 10.1021/bi00694a018 – ident: ref23/cit23 doi: 10.1042/BJ20131386 – ident: ref51/cit51 doi: 10.1021/ja01111a052 – ident: ref24/cit24 doi: 10.1111/bjh.14421 – ident: ref42/cit42 doi: 10.1107/S0907444913000061 – ident: ref73/cit73 doi: 10.1021/bi981698k – ident: ref37/cit37 doi: 10.1021/ja971756+ – ident: ref94/cit94 doi: 10.1042/bj2580599 – ident: ref83/cit83 doi: 10.1016/0005-2795(81)90217-8 – ident: ref93/cit93 doi: 10.1042/bj2580595 – ident: ref20/cit20 doi: 10.1021/acs.biochem.7b00890 – ident: ref84/cit84 doi: 10.1016/0005-2728(76)90081-5 – volume: 253 start-page: 8420 year: 1978 ident: ref89/cit89 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(17)34308-9 contributor: fullname: Drew H. R. – ident: ref53/cit53 doi: 10.1046/j.1432-1327.2001.02335.x – volume: 249 start-page: 2624 year: 1974 ident: ref81/cit81 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)42776-2 contributor: fullname: Davis L. A. – start-page: 1 volume-title: Cytochromes b and c: biochemical properties, biological functions and electrochemical analysis year: 2014 ident: ref2/cit2 contributor: fullname: Hütteman M. – volume: 257 start-page: 2267 year: 1982 ident: ref38/cit38 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)34916-0 contributor: fullname: Dyson H. J. – ident: ref85/cit85 doi: 10.1042/bj2460043 – ident: ref52/cit52 doi: 10.1107/S0907444909042073 – ident: ref62/cit62 doi: 10.1021/acs.biochem.8b00520 – ident: ref72/cit72 doi: 10.1002/bip.22164 – ident: ref22/cit22 doi: 10.1021/ja106328k – ident: ref10/cit10 doi: 10.1073/pnas.1323828111 – ident: ref6/cit6 doi: 10.1021/bi701237b – ident: ref44/cit44 doi: 10.1107/S2059798317016035 – ident: ref31/cit31 doi: 10.1021/bi048218b – ident: ref36/cit36 doi: 10.1042/bj0710570 – ident: ref39/cit39 doi: 10.1021/bi700992y – ident: ref13/cit13 doi: 10.1038/ng.103 – ident: ref19/cit19 doi: 10.1038/srep30447 – ident: ref34/cit34 doi: 10.1021/bi00421a014 – ident: ref76/cit76 doi: 10.1016/S0006-3495(98)74000-7 – ident: ref64/cit64 doi: 10.1021/acs.biochem.9b00295 – ident: ref78/cit78 doi: 10.1007/s00775-018-1603-3 – ident: ref43/cit43 doi: 10.1107/S0907444909042589 – ident: ref79/cit79 doi: 10.1021/acs.jpcb.6b01497 – ident: ref12/cit12 doi: 10.1039/c1ob05552f – ident: ref46/cit46 doi: 10.1107/S0907444911001314 – ident: ref4/cit4 doi: 10.1146/annurev.biochem.73.011303.073706 – ident: ref60/cit60 doi: 10.1007/s00775-014-1174-x – ident: ref66/cit66 doi: 10.1021/bi000266i – ident: ref7/cit7 doi: 10.1101/gad.272278.115 – ident: ref15/cit15 doi: 10.1016/j.bbadis.2013.12.002 – ident: ref61/cit61 doi: 10.1021/ja9717572 – ident: ref95/cit95 doi: 10.1021/bi00434a012 – ident: ref3/cit3 doi: 10.1016/S0092-8674(00)80085-9 – ident: ref68/cit68 doi: 10.1016/j.jmb.2006.04.035 – ident: ref86/cit86 doi: 10.1038/nature06407 – ident: ref32/cit32 doi: 10.1021/bi034958t – ident: ref49/cit49 doi: 10.1016/0003-2697(72)90451-4 – ident: ref80/cit80 doi: 10.1021/jp963142h – ident: ref25/cit25 doi: 10.1016/S0022-2836(03)00697-1 – start-page: 611 volume-title: Cytochrome c: A Multidisciplinary Approach year: 1996 ident: ref56/cit56 contributor: fullname: Wilson M. T. – ident: ref77/cit77 doi: 10.1021/acs.accounts.5b00106 – ident: ref87/cit87 doi: 10.1038/nature06522 – ident: ref48/cit48 doi: 10.1107/S0907444910007493 – ident: ref70/cit70 doi: 10.1016/j.jmb.2004.08.005 – ident: ref21/cit21 doi: 10.1007/s00775-012-0973-1 – ident: ref11/cit11 doi: 10.1021/jacs.6b10745 – ident: ref27/cit27 doi: 10.1021/bi016060e – ident: ref45/cit45 doi: 10.1021/acs.biochem.7b00342 – ident: ref63/cit63 doi: 10.1016/j.bbrc.2004.11.105 – ident: ref26/cit26 doi: 10.1016/j.bbrc.2003.10.182 |
| SSID | ssj0025286 |
| Score | 2.459546 |
| Snippet | The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of... The A51V variant of human cytochrome is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of the... The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 Å structure of... |
| SourceID | pubmedcentral proquest crossref pubmed acs |
| SourceType | Open Access Repository Aggregation Database Index Database Publisher |
| StartPage | 8939 |
| Title | Naturally Occurring A51V Variant of Human Cytochrome c Destabilizes the Native State and Enhances Peroxidase Activity |
| URI | http://dx.doi.org/10.1021/acs.jpcb.9b05869 https://www.ncbi.nlm.nih.gov/pubmed/31557440 https://search.proquest.com/docview/2299148767 https://pubmed.ncbi.nlm.nih.gov/PMC6813825 |
| Volume | 123 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LT-MwELZ4HJYLj4WF8tKsBIc9pJvYTuIcqwqEkKhWWkDcIsd2VHZRikh6gF_PjNMWCghxdRJLnpn4-8ZjfcPYkUx1IiId4-6XyUBq4YIiFDKw1JsKEdsITRXdi0FydiXPb-KbF5mctxV8Hv3Wpu7-uzdFNyvCWCXZIlvmdIGQaFD_7yy5irnv6ohwROlQOC1JfjQDAZGp54HoHbt8e0nyFeqcrrXti2ovVkiXTf53x03RNU_vpRy_sKB1tjohn9Bro2WDLbjqO_vWn_Z822TjgfY6HHePQPLDD3ToB704uoZrzKnRCTAqwZ_7Q_-xGZkhiR2AAcpevVTvk6sBKSUMvJ44eCoLurJwUg0pvmr443AttxbBE3qmbV2xxa5OTy77Z8GkMUOgpRBNgCRSlxyJZeKy0gprJOY9nBskW9K4WITKSJk6VxJhFDoprLYll4WVqlBR4sQPtlSNKrfDwLgIN1j8WpRKKl1mQoXS4kw4pEIdddgx2iuf_Fh17mvmPMr9IBoxnxixw35NvZnftzodn7z7c-ruHO1LFRJdudG4zjmCM-aHaZJ22Hbr_tlsApkXqSl2WDoXGLMXSKh7_kl1O_SC3Ykipcd494tr2WMrSMsyQkgu99lS8zB2B0h9muLQx_wzzRgAMw |
| link.rule.ids | 230,315,786,790,891,2782,27109,27957,27958,57093,57143 |
| linkProvider | American Chemical Society |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3fb9MwED6N7WG8wMbPwhiHBA88pEtiJ3Eeq2pTB1uFYJv2Fjm2ow5QOi3pw_bXc-c2hW4TglfHOdnns--7nPMdwHuZ6VREOqHTL5eB1MIFZShkYLk2FXlsIzRndI_H6ehUfjpPztcg6v6FoUE0JKnxSfzf7ALRHrd9vzRlPy_DRKX5A9hIMgrHGQ0Nvy1jrCT2xR3JK3FUFHaZyfsksD8yzao_ugMyb9-V_MP5HDyGr8th-zsnP_qztuybm1uMjv81ry14tICiOJjbzjasufoJbA67CnBPYTbWnpXj5zUyGfEVfwLEQRKd4RlF2LQkOK3QZwFweN1OzYSpD9Agx7KeuPfGNUgAE8eeXRw9sEVdW9yvJ2xtDX5xNKULS64UB2ZeyOIZnB7snwxHwaJMQ6ClEG1AkFJXMcHM1OWVFdZIioLi2BD0ksYlIlRGysy5iuGj0Glpta1iWVqpShWlTjyH9Xpau5eAxkV03NLbolJS6SoXKpSWJFGTCnXUgw-kr2KxzZrCZ9DjqPCNpMRiocQefOwWtbics3b8pe-7btUL0i_nS3TtprOmiMlVU7SYpVkPXsytYClNEA5jbsUeZCv2sezAtN2rT-qLiafvThXzPiav_nEub2FzdHJ8VBwdjj-_hocE2HL2nbHcgfX2aubeEChqy12_DX4BwhUIng |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3dT9swED8xkLa9APvuBpsnbQ97SJfEduI8VoWKfVVIGxVvkWM7KtuUViR9gL-eOzepKKCJvTrOyT6ffb_LOb8D-CBSnfBISzz9MhEIzV1QhFwElmpTocc2XFNG98c4OToRX0_l6QbI7l8YHESNkmqfxKddPbdlyzAQfab233NT9LMilCrJHsCWpPrdhIiGP1dxlox9gUf0TBQZhV128i4J5JNMve6TbgHNm_clrzmg0Q5MVkP3907-9BdN0TeXN1gd_3tuu7DdQlI2WNrQE9hw1VN4NOwqwT2DxVh7do6_F4xIic_pUyAbyGjCJhhp49KwWcl8NoANL5qZmRIFAjOMYlpP4HvpaoZAk409yzjzAJfpyrLDakpWV7Njh9M6s-hS2cAsC1o8h5PR4a_hUdCWawi04LwJEFrqMka4mbistNwagdFQHBuEYMI4yUNlhEidKwlGcp0UVtsyFoUVqlBR4vgL2KxmlXsFzLgIj118m5dKKF1mXIXCoiRsUqGOevAR9ZW3263OfSY9jnLfiErMWyX24FO3sPl8yd7xj77vu5XPUb-UN9GVmy3qPEaXjVFjmqQ9eLm0hJU0jniMOBZ7kK7ZyKoD0XevP6nOpp7GO1HE_yhf33Mu7-Dh8cEo__5l_O0NPEbclpELjcUebDbnC7eP2Kgp3vqdcAUhFwsY |
| 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=Naturally+Occurring+A51V+Variant+of+Human+Cytochrome+c+Destabilizes+the+Native+State+and+Enhances+Peroxidase+Activity&rft.jtitle=The+journal+of+physical+chemistry.+B&rft.au=Lei%2C+Haotian&rft.au=Bowler%2C+Bruce+E&rft.date=2019-10-24&rft.eissn=1520-5207&rft.volume=123&rft.issue=42&rft.spage=8939&rft.epage=8953&rft_id=info:doi/10.1021%2Facs.jpcb.9b05869&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1520-6106&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1520-6106&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1520-6106&client=summon |