A look inside HIV resistance through retroviral protease interaction maps.
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.
Kontijevskis
Aleksejs
A
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Prusis
Peteris
P
Petrovska
Ramona
R
Yahorava
Sviatlana
S
Mutulis
Felikss
F
Mutule
Ilze
I
Komorowski
Jan
J
Wikberg
Jarl E S
JE
D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D024882:Drug Resistance, Viral / Q000502:physiology*; D015497:HIV-1 / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D012190:Retroviridae / Q000201:enzymology*; D012191:Retroviridae Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
D012191:Retroviridae Proteins; D010447:Peptide Hydrolases