ISSN:
0887-3585
Schlagwort(e):
aspartic protease
;
HIV-1
;
molecular dynamics
;
molecular modeling
;
Chemistry
;
Biochemistry and Biotechnology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Medizin
Notizen:
Six models of the catalytic site of HIV-1 protease complexed with a reduced peptide inhibitor, MVT-101, were investigated. These studies focused on the details of protonation of the active site, its total net charge and hydrogen bonding pattern, which was consistent with both the observed coplanar configuration of the acidic groups of the catalytic aspartates (Asp-25 and Asp-125) and the observed binding mode of the inhibitor. Molecular dynamic simulations using AMBER 4.0 indicated that the active site should be neutral. The planarity of the aspartate dyad may be due to the formation of two hydrogen bonds: one between the inner Oδ1oxygen atoms of the two catalytic aspartates and another between the Oδ2atom of Asp-125 and the nitrogen atom of the reduced peptide bond of the bound inhibitor. This would require two additional protonations, either of both aspartates, or of one Asp and the amido nitrogen atom of Nle-204. Our results favor the Asp-inhibitor protonation but the other one is not excluded. Implications of these findings for the mechanism of enzymatic catalysis are discussed. Dynamic properties of the hydrogen bond network in the active site and an analysis of the interaction energy between the inhibitor and the protease are presented. © 1997 Wiley-Liss, Inc.
Zusätzliches Material:
3 Ill.
Materialart:
Digitale Medien
