Journal article
Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones
Molecular and biochemical parasitology, v 58(1)
1993
PMID: 8459834
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones
- Creators
- Akhil B Vaidya - Malaria Research Group, Department of Microbiology and Immunology, Hahnemann University, Philadelphia, PA, USAMonir S Lashgari - Malaria Research Group, Department of Microbiology and Immunology, Hahnemann University, Philadelphia, PA, USALaura G Pologe - Department of Medical and Molecular Parasitology, New York University, New York, NY, USAJoanne Morrisey - Malaria Research Group, Department of Microbiology and Immunology, Hahnemann University, Philadelphia, PA, USA
- Publication Details
- Molecular and biochemical parasitology, v 58(1)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:A1993KM98700005
- Scopus ID
- 2-s2.0-0027463776
- Other Identifier
- 991014878578204721
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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