1A5W

ASV INTEGRASE CORE DOMAIN WITH HIV-1 INTEGRASE INHIBITOR Y3

Summary for 1A5W

• Entry DOI: 10.2210/pdb1a5w/pdb
• Descriptor: INTEGRASE, 4-ACETYLAMINO-5-HYDROXYNAPHTHALENE-2,7-DISULFONIC ACID (3 entities in total)
• Functional Keywords: hydrolase, endonuclease, hiv-1 integrase inhibitor
• Biological source: Rous sarcoma virus (strain Schmidt-Ruppin)
• Cellular location: Matrix protein p19: Virion (Potential). Capsid protein p27: Virion (Potential). Nucleocapsid protein p12: Virion (Potential): P03354
• Total number of polymer chains: 1
• Total formula weight: 17760.27

Authors

Lubkowski, J.,Yang, F.,Alexandratos, J.,Wlodawer, A. (deposition date: 1998-02-18, release date: 1998-05-27, Last modification date: 2024-05-22)

Primary citation

Lubkowski, J.,Yang, F.,Alexandratos, J.,Wlodawer, A.,Zhao, H.,Burke Jr., T.R.,Neamati, N.,Pommier, Y.,Merkel, G.,Skalka, A.M.
Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.
Proc.Natl.Acad.Sci.USA, 95:4831-4836, 1998

PubMed Abstract: 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.

PubMed: 9560188
DOI: 10.1073/pnas.95.9.4831

Experimental method

X-RAY DIFFRACTION (2 Å)