| pubmed-article:20852643 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C0043474 | lld:lifeskim |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C0728940 | lld:lifeskim |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C0678594 | lld:lifeskim |
| pubmed-article:20852643 | lifeskim:mentions | umls-concept:C1527178 | lld:lifeskim |
| pubmed-article:20852643 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:20852643 | pubmed:dateCreated | 2010-10-6 | lld:pubmed |
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| pubmed-article:20852643 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:abstractText | Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate (AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision. | lld:pubmed |
| pubmed-article:20852643 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20852643 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20852643 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20852643 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:20852643 | pubmed:issn | 1545-9985 | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:HughesStephen... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:DasKalyanK | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:ArnoldEddyE | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:BoyerPaul LPL | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:SarafianosSte... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:TuXiongyingX | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:JonesRoger... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:BaumanJoseph... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:ClarkArthur... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:GaffneyBarbar... | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:HouXiaorongX | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:HanQianweiQ | lld:pubmed |
| pubmed-article:20852643 | pubmed:author | pubmed-author:FrenkelYulia... | lld:pubmed |
| pubmed-article:20852643 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20852643 | pubmed:volume | 17 | lld:pubmed |
| pubmed-article:20852643 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20852643 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20852643 | pubmed:pagination | 1202-9 | lld:pubmed |
| pubmed-article:20852643 | pubmed:dateRevised | 2010-12-3 | lld:pubmed |
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| pubmed-article:20852643 | pubmed:meshHeading | pubmed-meshheading:20852643... | lld:pubmed |
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| pubmed-article:20852643 | pubmed:meshHeading | pubmed-meshheading:20852643... | lld:pubmed |
| pubmed-article:20852643 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20852643 | pubmed:articleTitle | Structural basis of HIV-1 resistance to AZT by excision. | lld:pubmed |
| pubmed-article:20852643 | pubmed:affiliation | Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey, USA. | lld:pubmed |
| pubmed-article:20852643 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20852643 | lld:pubmed |
