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Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 95(9)
- Publication Year :
- 1998
-
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-Å resolution at two pH values, with and without Mn 2+ 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.
- Subjects :
- Models, Molecular
Stereochemistry
Molecular Sequence Data
Crystallography, X-Ray
Avian sarcoma virus
Divalent
Metal
Naphthalenesulfonates
Hydrolase
Molecule
HIV Integrase Inhibitors
Binding site
chemistry.chemical_classification
Manganese
Multidisciplinary
Binding Sites
biology
Integrases
Active site
Hydrogen-Ion Concentration
Biological Sciences
Integrase
Protein Structure, Tertiary
chemistry
Biochemistry
Avian Sarcoma Viruses
visual_art
visual_art.visual_art_medium
biology.protein
Subjects
Details
- ISSN :
- 00278424
- Volume :
- 95
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....13ff9e9339d880485ae52b63e79f081b