We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2aog

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2aog.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2aog.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2aog| PDB=2aog | SCENE= }}
{{STRUCTURE_2aog| PDB=2aog | SCENE= }}
-
'''Crystal structure analysis of HIV-1 protease mutant V82A with a substrate analog P2-NC'''
+
===Crystal structure analysis of HIV-1 protease mutant V82A with a substrate analog P2-NC===
-
==Overview==
+
<!--
-
HIV-1 protease (PR) and two drug-resistant variants--PR with the V82A mutation (PR(V82A)) and PR with the I84V mutation (PR(I84V))--were studied using reduced peptide analogs of five natural cleavage sites (CA-p2, p2-NC, p6pol-PR, p1-p6 and NC-p1) to understand the structural and kinetic changes. The common drug-resistant mutations V82A and I84V alter residues forming the substrate-binding site. Eight crystal structures were refined at resolutions of 1.10-1.60 A. Differences in the PR-analog interactions depended on the peptide sequence and were consistent with the relative inhibition. Analog p6(pol)-PR formed more hydrogen bonds of P2 Asn with PR and fewer van der Waals contacts at P1' Pro compared with those formed by CA-p2 or p2-NC in PR complexes. The P3 Gly in p1-p6 provided fewer van der Waals contacts and hydrogen bonds at P2-P3 and more water-mediated interactions. PR(I84V) showed reduced van der Waals interactions with inhibitor compared with PR, which was consistent with kinetic data. The structures suggest that the binding affinity for mutants is modulated by the conformational flexibility of the substrate analogs. The complexes of PR(V82A) showed smaller shifts of the main chain atoms of Ala82 relative to PR, but more movement of the peptide analog, compared to complexes with clinical inhibitors. PR(V82A) was able to compensate for the loss of interaction with inhibitor caused by mutation, in agreement with kinetic data, but substrate analogs have more flexibility than the drugs to accommodate the structural changes caused by mutation. Hence, these structures help to explain how HIV can develop drug resistance while retaining the ability of PR to hydrolyze natural substrates.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16218957}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16218957 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16218957}}
==About this Structure==
==About this Structure==
Line 36: Line 40:
[[Category: Mutant]]
[[Category: Mutant]]
[[Category: Substrate analog]]
[[Category: Substrate analog]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:17:21 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:10:44 2008''

Revision as of 08:10, 28 July 2008

Image:2aog.png

Template:STRUCTURE 2aog

Crystal structure analysis of HIV-1 protease mutant V82A with a substrate analog P2-NC

Template:ABSTRACT PUBMED 16218957

About this Structure

2AOG is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

Reference

Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs., Tie Y, Boross PI, Wang YF, Gaddis L, Liu F, Chen X, Tozser J, Harrison RW, Weber IT, FEBS J. 2005 Oct;272(20):5265-77. PMID:16218957

Page seeded by OCA on Mon Jul 28 11:10:44 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2aog"
Personal tools