| pubmed-article:20937817 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C0243044 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C1136102 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C0598312 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C1825534 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C1999216 | lld:lifeskim |
| pubmed-article:20937817 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:20937817 | pubmed:issue | 50 | lld:pubmed |
| pubmed-article:20937817 | pubmed:dateCreated | 2010-12-6 | lld:pubmed |
| pubmed-article:20937817 | pubmed:abstractText | Chemical genetics is an emerging approach to investigate the biology of host-pathogen interactions. We screened several inhibitors of ATP-dependent DNA motors and detected the gyrase B inhibitor coumermycin A1 (C-A1) as a potent antiretroviral. C-A1 inhibited HIV-1 integration and gene expression from acutely infected cell, but the two activities mapped to distinct targets. Target discovery identified Hsp90 as the C-A1 target affecting viral gene expression. Chromatin immunoprecipitation revealed that Hsp90 associates with the viral promoter and may directly regulate gene expression. Molecular docking suggested that C-A1 binds to two novel pockets at the C terminal domain of Hsp90. C-A1 inhibited Hsp90 dimer formation, suggesting that it impairs viral gene expression by preventing Hsp90 dimerization at the C terminus. The inhibition of HIV-1 integration imposed by C-A1 was independent of Hsp90 and mapped to the capsid protein, and a point mutation at residue 105 made the virus resistant to this block. HIV-1 susceptibility to the integration block mediated by C-A1 was influenced by cyclophilin A. Our chemical genetic approach revealed an unexpected function of capsid in HIV-1 integration and provided evidence for a role of Hsp90 in regulating gene expression in mammalian cells. Both activities were amenable to inhibition by small molecules and represent novel antiretroviral drug targets. | lld:pubmed |
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| pubmed-article:20937817 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20937817 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20937817 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20937817 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20937817 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20937817 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:20937817 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20937817 | pubmed:author | pubmed-author:AndersonIanI | lld:pubmed |
| pubmed-article:20937817 | pubmed:author | pubmed-author:JennerRichard... | lld:pubmed |
| pubmed-article:20937817 | pubmed:author | pubmed-author:FassatiAriber... | lld:pubmed |
| pubmed-article:20937817 | pubmed:author | pubmed-author:SelwoodDavidD | lld:pubmed |
| pubmed-article:20937817 | pubmed:author | pubmed-author:ZhouLihongL | lld:pubmed |
