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dc.contributor.authorJohnson, Allison A.
dc.contributor.authorSantos, Webster
dc.contributor.authorPais, Godwin C. G.
dc.contributor.authorMarchand, Christophe
dc.contributor.authorAmin, Ronak
dc.contributor.authorBurke, Terrence R.
dc.contributor.authorVerdine, Gregory
dc.contributor.authorPommier, Yves
dc.date.accessioned2019-10-09T13:56:34Z
dc.date.issued2006
dc.identifier.citationJohnson, Allison A., Webster Santos, Godwin C. G. Pais, Christophe Marchand, Ronak Amin, Terrence R. Burke, Gregory Verdine, and Yves Pommier. 2006. “Integration Requires a Specific Interaction of the Donor DNA Terminal 5′-Cytosine with Glutamine 148 of the HIV-1 Integrase Flexible Loop.” Journal of Biological Chemistry281 (1): 461–67. https://doi.org/10.1074/jbc.M511348200.
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41511259*
dc.description.abstractIntegration is essential for retroviral replication and gene therapy using retroviral vectors. Human immunodeficiency virus, type 1 (HIV-1), integrase specifically recognizes the terminal sequences of each long terminal repeat ( LTR) and cleaves the 3'-end terminal dinucleotide 5'-GT. The exposed 3'-hydroxyl is then positioned for nucleophilic attack and subsequent strand transfer into another DNAduplex (target or chromosomal DNA). We report that both the terminal cytosine at the protruding 5'-end of the long terminal repeats (5'-C) and the integrase residue Gln-148 are critical for strand transfer. Proximity of the 5'-C and Gln-148 was demonstrated by disulfide cross-linking. Cross- linking is inhibited by the inhibitor 5CITEP 1-( 5- chloroindol- 3- yl)- 3- hydroxy- 3-(2H-tetrazol-5- yl)- propenone. We propose that strand transfer requires a conformational change of the integrase-viral (donor) DNA-complex with formation of an H-bond between the N-3 of the 5'-C and the amine group of Gln-148. These findings have implications for the molecular mechanisms coupling 3'-processing and strand transfer as well as for the molecular pharmacology of integrase inhibitors.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dash.licenseLAA
dc.titleIntegration Requires a Specific Interaction of the Donor DNA Terminal 5′-Cytosine with Glutamine 148 of the HIV-1 Integrase Flexible Loop
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Biological Chemistry
dash.depositing.authorVerdine, Gregory L.::b80a6eb8a9fb2d98773ce5b5cc1dd993::600
dc.date.available2019-10-09T13:56:34Z
dash.workflow.comments1Science Serial ID 106391
dc.identifier.doi10.1074/jbc.M511348200
dash.source.volume281;1
dash.source.page461-467


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