Source:http://linkedlifedata.com/resource/pubmed/id/16075307
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2005-8-2
|
| pubmed:abstractText |
We report structural models of the full-length integrase enzyme (IN) of the human immunodeficiency virus type 1 (HIV-1) and its complex with viral and human DNA. These were developed by means of molecular modeling techniques using all available experimental evidence, including X-ray crystallographic and NMR structures of portions of the full-length protein. Special emphasis was placed on obtaining a model of the enzyme's active site with the viral DNA apposed to it, based on the hypothesis that such a model would allow structure-based design of inhibitors that retain activity in vivo. This was because bound DNA might be present in vivo after 3'-processing but before strand transfer. These structural models were used to study the potential binding modes of various diketo-acid HIV-1 IN inhibitors (many of them preferentially inhibiting strand transfer) for which no experimentally derived complexed structures are available. The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Integrase,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0920-654X
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
18
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
739-60
|
| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16075307-Amino Acid Sequence,
pubmed-meshheading:16075307-Anti-HIV Agents,
pubmed-meshheading:16075307-Base Sequence,
pubmed-meshheading:16075307-Binding Sites,
pubmed-meshheading:16075307-Computer Simulation,
pubmed-meshheading:16075307-Crystallography, X-Ray,
pubmed-meshheading:16075307-DNA,
pubmed-meshheading:16075307-DNA, Viral,
pubmed-meshheading:16075307-Drug Design,
pubmed-meshheading:16075307-HIV Integrase,
pubmed-meshheading:16075307-HIV-1,
pubmed-meshheading:16075307-Humans,
pubmed-meshheading:16075307-Macromolecular Substances,
pubmed-meshheading:16075307-Models, Molecular,
pubmed-meshheading:16075307-Molecular Sequence Data,
pubmed-meshheading:16075307-Molecular Structure,
pubmed-meshheading:16075307-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:16075307-Protein Structure, Tertiary,
pubmed-meshheading:16075307-Static Electricity
|
| pubmed:year |
2004
|
| pubmed:articleTitle |
Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design.
|
| pubmed:affiliation |
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA. mn1@helix.nih.gov
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| pubmed:publicationType |
Journal Article,
In Vitro
|