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- Title
A Look Inside HIV Resistance through Retroviral Protease Interaction Maps.
- Authors
Kontijevskis, Aleksejs; Prusis, Peteris; Petrovska, Ramona; Yahorava, Sviatlana; Mutulis, Felikss; Mutule, Ilze; Komorowski, Jan; Wikberg, Jarl E. S.
- Abstract
Retroviruses affect a large number of species, from fish and birds to mammals and humans, with global socioeconomic negative impacts. Here the authors report and experimentally validate a novel approach for the analysis of the molecular networks that are involved in the recognition of substrates by retroviral proteases. Using multivariate analysis of the sequence-based physiochemical descriptions of 61 retroviral proteases comprising wild-type proteases, natural mutants, and drug-resistant forms of proteases from nine different viral species in relation to their ability to cleave 299 substrates, the authors mapped the physicochemical properties and cross-dependencies of the amino acids of the proteases and their substrates, which revealed a complex molecular interaction network of substrate recognition and cleavage. The approach allowed a detailed analysis of the molecular-chemical mechanisms involved in substrate cleavage by retroviral proteases.
- Subjects
RETROVIRUS enzymes; HIV virus enzymes; PROTEOLYTIC enzymes; DRUG resistance; AMINO acids
- Publication
PLoS Computational Biology, 2007, Vol 3, Issue 3, p0424
- ISSN
1553-734X
- Publication type
Article
- DOI
10.1371/journal.pcbi.0030048