1a5x
ASV INTEGRASE CORE DOMAIN WITH HIV-1 INTEGRASE INHIBITOR Y3
|
OverviewOverview
The x-ray structures of an inhibitor complex of the catalytic core domain, of avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-A, resolution at two pH values, with and without Mn2+ cations. This inhibitor, (Y-3), originally identified in a screen for inhibitors of the catalytic, activity of HIV type 1 integrase (HIV-1 IN), was found in the present, study to be active against ASV IN as well as HIV-1 IN. The Y-3 molecule is, located in close proximity to the enzyme active site, interacts with the, flexible loop, alters loop conformation, and affects the conformations of, active site residues. As crystallized, a Y-3 molecule stacks against its, symmetry-related mate. Preincubation of IN with metal cations does not, prevent inhibition, and Y-3 binding does not prevent binding of divalent, cations to IN. Three compounds chemically related to Y-3 also were, investigated, but no binding was observed in the crystals. Our results, identify the structural elements of the inhibitor that likely determine, its binding properties.
About this StructureAbout this Structure
1A5X is a Single protein structure of sequence from Rous sarcoma virus with Y3 as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor., Lubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR Jr, Neamati N, Pommier Y, Merkel G, Skalka AM, Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4831-6. PMID:9560188
Page seeded by OCA on Tue Dec 18 14:09:36 2007