Structural insights into Plasmodium PPIases

Malaria is one of the most prevalent infectious diseases posing a serious challenge over the years, mainly owing to the emergence of drug-resistant strains, sparking a need to explore and identify novel protein targets. It is a well-known practice to adopt a chemo-genomics approach towards identifyi...

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Published inFrontiers in cellular and infection microbiology Vol. 12; p. 931635
Main Authors Rajan, Sreekanth, Yoon, Ho Sup
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 02.09.2022
Subjects
Cellular and Infection Microbiology
cyclophilin
FK506
FKBP
malaria
plasmodium
PPIase
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Abstract Malaria is one of the most prevalent infectious diseases posing a serious challenge over the years, mainly owing to the emergence of drug-resistant strains, sparking a need to explore and identify novel protein targets. It is a well-known practice to adopt a chemo-genomics approach towards identifying targets for known drugs, which can unravel a novel mechanism of action to aid in better drug targeting proficiency. Immunosuppressive drugs cyclosporin A, FK506 and rapamycin, were demonstrated to inhibit the growth of the malarial parasite, Plasmodium falciparum . Peptidyl prolyl cis/trans isomerases (PPIases), comprising cylcophilins and FK506-binding proteins (FKBPs), the specific target of these drugs, were identified in the Plasmodium parasite and proposed as an antimalarial drug target. We previously attempted to decipher the structure of these proteins and target them with non-immunosuppressive drugs, predominantly on FKBP35. This review summarizes the structural insights on Plasmodium PPIases, their inhibitor complexes and perspectives on drug discovery.
AbstractList Malaria is one of the most prevalent infectious diseases posing a serious challenge over the years, mainly owing to the emergence of drug-resistant strains, sparking a need to explore and identify novel protein targets. It is a well-known practice to adopt a chemo-genomics approach towards identifying targets for known drugs, which can unravel a novel mechanism of action to aid in better drug targeting proficiency. Immunosuppressive drugs cyclosporin A, FK506 and rapamycin, were demonstrated to inhibit the growth of the malarial parasite, Plasmodium falciparum. Peptidyl prolyl cis/trans isomerases (PPIases), comprising cylcophilins and FK506-binding proteins (FKBPs), the specific target of these drugs, were identified in the Plasmodium parasite and proposed as an antimalarial drug target. We previously attempted to decipher the structure of these proteins and target them with non-immunosuppressive drugs, predominantly on FKBP35. This review summarizes the structural insights on Plasmodium PPIases, their inhibitor complexes and perspectives on drug discovery.
Malaria is one of the most prevalent infectious diseases posing a serious challenge over the years, mainly owing to the emergence of drug-resistant strains, sparking a need to explore and identify novel protein targets. It is a well-known practice to adopt a chemo-genomics approach towards identifying targets for known drugs, which can unravel a novel mechanism of action to aid in better drug targeting proficiency. Immunosuppressive drugs cyclosporin A, FK506 and rapamycin, were demonstrated to inhibit the growth of the malarial parasite, Plasmodium falciparum . Peptidyl prolyl cis/trans isomerases (PPIases), comprising cylcophilins and FK506-binding proteins (FKBPs), the specific target of these drugs, were identified in the Plasmodium parasite and proposed as an antimalarial drug target. We previously attempted to decipher the structure of these proteins and target them with non-immunosuppressive drugs, predominantly on FKBP35. This review summarizes the structural insights on Plasmodium PPIases, their inhibitor complexes and perspectives on drug discovery.
Author Yoon, Ho Sup
Rajan, Sreekanth
AuthorAffiliation 3 CHA Advanced Research Institute , Seongnam-si , South Korea
1 School of Biological Sciences, Nanyang Technological University , Singapore , Singapore
2 College of Pharmacy, CHA University , Pocheon-si , South Korea
AuthorAffiliation_xml – name: 2 College of Pharmacy, CHA University , Pocheon-si , South Korea
– name: 1 School of Biological Sciences, Nanyang Technological University , Singapore , Singapore
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  surname: Rajan
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  givenname: Ho Sup
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Edited by: Felix Hausch, Darmstadt University of Technology, Germany
Reviewed by: Thomas Atack, Broad Institute, United States; Manish Chauhan, Washington State University, United States
This article was submitted to Bacteria and Host, a section of the journal Frontiers in Cellular and Infection Microbiology
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Snippet Malaria is one of the most prevalent infectious diseases posing a serious challenge over the years, mainly owing to the emergence of drug-resistant strains,...
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SubjectTerms Cellular and Infection Microbiology
cyclophilin
FK506
FKBP
malaria
plasmodium
PPIase
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Title Structural insights into Plasmodium PPIases
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https://pubmed.ncbi.nlm.nih.gov/PMC9478106
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Volume 12
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