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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2002-11-28
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pubmed:abstractText |
AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the nucleotide-binding site (pre-translocation complex N) but not at the 'priming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 A resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12456667-10322129,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/12456667-9857206
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pubmed:language |
eng
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:author |
pubmed-author:ArnoldEddyE,
pubmed-author:BirktoftJens JJJ,
pubmed-author:BoyerPaul LPL,
pubmed-author:ClarkArthur DADJr,
pubmed-author:CorinEllenE,
pubmed-author:DasKalyanK,
pubmed-author:HughesStephen HSH,
pubmed-author:IlankumaranPalanichamyP,
pubmed-author:JerinaDonald MDM,
pubmed-author:LeftonR SRS,
pubmed-author:SarafianosStefan GSG,
pubmed-author:TuskeSteveS
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6614-24
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pubmed:dateRevised |
2009-11-18
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pubmed:articleTitle |
Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA.
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pubmed:affiliation |
Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA.
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