pubmed-article:20610719 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C1273518 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0376601 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0683598 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
pubmed-article:20610719 | lifeskim:mentions | umls-concept:C0917728 | lld:lifeskim |
pubmed-article:20610719 | pubmed:issue | 18 | lld:pubmed |
pubmed-article:20610719 | pubmed:dateCreated | 2010-8-19 | lld:pubmed |
pubmed-article:20610719 | pubmed:abstractText | MK-2048 represents a prototype second-generation integrase strand transfer inhibitor (INSTI) developed with the goal of retaining activity against viruses containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. These mutations were selected in vitro and confirmed by site-specific mutagenesis. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. The subsequent selection of E138K partially restored replication capacity to approximately 13% of wt levels and increased resistance to MK-2048 to approximately 8-fold. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer "off" rate of MK-2048. In silico structural analysis suggests that the introduction of a positively charged arginine at position 118, near the catalytic amino acid 116, might decrease Mg(2+) binding, compromising enzyme function and thus leading to the significant reduction in both integration and viral replication capacity observed with these mutations. | lld:pubmed |
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pubmed-article:20610719 | pubmed:language | eng | lld:pubmed |
pubmed-article:20610719 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20610719 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20610719 | pubmed:month | Sep | lld:pubmed |
pubmed-article:20610719 | pubmed:issn | 1098-5514 | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:OliveiraMaure... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:WainbergMark... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:HazudaDaria... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:XuHongtaoH | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:Bar-MagenTama... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:SloanRichard... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:DonahueDaniel... | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:KuhlBjörn DBD | lld:pubmed |
pubmed-article:20610719 | pubmed:author | pubmed-author:ZabeidaAlexan... | lld:pubmed |
pubmed-article:20610719 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:20610719 | pubmed:volume | 84 | lld:pubmed |
pubmed-article:20610719 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:20610719 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:20610719 | pubmed:pagination | 9210-6 | lld:pubmed |
pubmed-article:20610719 | pubmed:dateRevised | 2011-7-25 | lld:pubmed |
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pubmed-article:20610719 | pubmed:meshHeading | pubmed-meshheading:20610719... | lld:pubmed |
pubmed-article:20610719 | pubmed:year | 2010 | lld:pubmed |
pubmed-article:20610719 | pubmed:articleTitle | Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. | lld:pubmed |
pubmed-article:20610719 | pubmed:affiliation | McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montréal, Quebec H3T 1E2, Canada. | lld:pubmed |
pubmed-article:20610719 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:20610719 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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