3ig1
HIV-1 Reverse Transcriptase with the Inhibitor beta-Thujaplicinol Bound at the RNase H Active SiteHIV-1 Reverse Transcriptase with the Inhibitor beta-Thujaplicinol Bound at the RNase H Active Site
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNovel inhibitors are needed to counteract the rapid emergence of drug-resistant HIV variants. HIV-1 reverse transcriptase (RT) has both DNA polymerase and RNase H (RNH) enzymatic activities, but approved drugs that inhibit RT target the polymerase. Inhibitors that act against new targets, such as RNH, should be effective against all of the current drug-resistant variants. Here, we present 2.80 A and 2.04 A resolution crystal structures of an RNH inhibitor, beta-thujaplicinol, bound at the RNH active site of both HIV-1 RT and an isolated RNH domain. beta-thujaplicinol chelates two divalent metal ions at the RNH active site. We provide biochemical evidence that beta-thujaplicinol is a slow-binding RNH inhibitor with noncompetitive kinetics and suggest that it forms a tropylium ion that interacts favorably with RT and the RNA:DNA substrate. Structure of HIV-1 reverse transcriptase with the inhibitor beta-Thujaplicinol bound at the RNase H active site.,Himmel DM, Maegley KA, Pauly TA, Bauman JD, Das K, Dharia C, Clark AD Jr, Ryan K, Hickey MJ, Love RA, Hughes SH, Bergqvist S, Arnold E Structure. 2009 Dec 9;17(12):1625-35. PMID:20004166[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||