5xn2: Difference between revisions
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==HIV-1 reverse transcriptase Q151M:DNA:dGTP ternary complex== | |||
<StructureSection load='5xn2' size='340' side='right' caption='[[5xn2]], [[Resolution|resolution]] 2.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5xn2]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XN2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGT:2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>DGT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zhr|4zhr]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xn2 OCA], [http://pdbe.org/5xn2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xn2 RCSB], [http://www.ebi.ac.uk/pdbsum/5xn2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xn2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hepatitis B virus (HBV) reverse transcriptase (RT) is essential for viral replication and is an important drug target. Nonetheless, the notorious insolubility of HBV RT has hindered experimental structural studies and structure-based drug design. Here, we demonstrate that a Q151M substitution alone at the nucleotide-binding site (N-site) of human immunodeficiency virus type-1 (HIV-1) RT renders HIV-1 highly sensitive to entecavir (ETV), a potent nucleoside analogue RT inhibitor (NRTI) against HBV. The results suggest that Met151 forms a transient hydrophobic interaction with the cyclopentyl methylene of ETV, a characteristic hydrophobic moiety of ETV. We thus solved the crystal structures of HIV-1 RT(Q151M):DNA complex with bound dGTP or ETV-triphosphate (ETV-TP). The structures revealed that ETV-TP is accommodated at the N-site slightly apart from the ribose ring of the 3'-end nucleotide, compared to the position of bound dGTP and previously reported NRTI/dNTP. In addition, the protruding methylene group of bound ETV-TP directly pushes the side-chain of Met184 backward. Met184 is a key residue that confers ETV resistance upon substitution with smaller Ile/Val. These results provide novel insights into NRTI binding to the N-site and further provide important clues for the development of novel anti-HBV/HIV-1 RT inhibitors to overcome critical drug resistance. | |||
HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir.,Yasutake Y, Hattori SI, Hayashi H, Matsuda K, Tamura N, Kohgo S, Maeda K, Mitsuya H Sci Rep. 2018 Jan 26;8(1):1624. doi: 10.1038/s41598-018-19602-9. PMID:29374261<ref>PMID:29374261</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5xn2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hayashi, H]] | |||
[[Category: Maeda, K]] | |||
[[Category: Tamura, N]] | [[Category: Tamura, N]] | ||
[[Category: Yasutake, Y]] | [[Category: Yasutake, Y]] | ||
[[Category: | [[Category: Drug resistance]] | ||
[[Category: Drug sensitivity]] | |||
[[Category: Entecavir]] | |||
[[Category: Hbv]] | |||
[[Category: Hiv-1]] | |||
[[Category: Reverse transcriptase]] | |||
[[Category: Transferase-dna complex]] | |||
Revision as of 06:15, 7 February 2018
HIV-1 reverse transcriptase Q151M:DNA:dGTP ternary complex
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