Logo image
Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones
Journal article   Peer reviewed

Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones

Akhil B Vaidya, Monir S Lashgari, Laura G Pologe and Joanne Morrisey
Molecular and biochemical parasitology, v 58(1)
1993
PMID: 8459834

Abstract

Plasmodium falciparum Mitochondrial DNA Cytochrome b Mitochondrial electron transport Antimalarial drugs
Appropriate functioning of mitochondria is critical for survival and growth of erythrocytic stages of malarial parasites, making it an attractive target for antimalarial drugs which may take advantage of unique features of parasite mitochondrial metabolism. We have sequenced the presumptive mitochondrial DNA, the 6-kb element, of Plasmodium falciparum, permitting an analysis of the predicted structure of parasite electron transport proteins. Although the overall structures of the 3 polypeptides, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3, and cytochrome b (cyt b), were similar to those from other species, some striking differences were observed, especially for the cyt b. Analysis of the cyt b structure showed that the critical quinone binding sites of the protein are quite divergent from those of other species. Comparative analysis suggests that these changes are the likely cause for the resistance of parasite cytochrome bc 1 complex to antimycin and related inhibitors. We suggest that the same features are responsible for increased affinity of the parasite cyt b for antimalarial compounds of class 8-aminoquinolines and hydroxynaphthoquinones, explaining the therapeutic value of these drugs.

Metrics

11 Record Views
109 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Parasitology
Logo image