View source for 6ika


==HIV-1 reverse transcriptase with Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L:DNA:entecavir-triphosphate ternary complex==
<StructureSection load='6ika' size='340' side='right'caption='[[6ika]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ika]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IKA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.598&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ET9:[[(1R,3S,5S)-3-(2-azanyl-6-oxidanylidene-3H-purin-9-yl)-2-methylidene-5-oxidanyl-cyclopentyl]methoxy-oxidanyl-phosphory+l]+phosphono+hydrogen+phosphate'>ET9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ika FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ika OCA], [https://pdbe.org/6ika PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ika RCSB], [https://www.ebi.ac.uk/pdbsum/6ika PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ika ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D3XFN7_9HIV1 D3XFN7_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nucleoside analogue reverse transcriptase (RT) inhibitors (NRTIs) are major antiviral agents against hepatitis B virus (HBV) and human immunodeficiency virus type-1 (HIV-1). However, the notorious insoluble property of HBV RT has prevented atomic-resolution structural studies and rational anti-HBV drug design. Here, we created HIV-1 RT mutants containing HBV-mimicking sextuple or septuple amino acid substitutions at the nucleoside-binding site (N-site) and verified that these mutants retained the RT activity. The most active RT mutant, HIV-1 RT(7MC), carrying Q151M/G112S/D113A/Y115F/F116Y/F160L/I159L was successfully crystallized, and its three-dimensional structure was determined in complex with DNA:dGTP/entecavir-triphosphate (ETV-TP), a potent anti-HBV guanosine analogue RT inhibitor, at a resolution of 2.43A and 2.60A, respectively. The structures reveal significant positional rearrangements of the amino acid side-chains at the N-site, elucidating the mechanism underlying the differential susceptibility of HIV-1 and HBV against recently reported 4'-modified NRTIs.

Active-site deformation in the structure of HIV-1 RT with HBV-associated septuple amino acid substitutions rationalizes the differential susceptibility of HIV-1 and HBV against 4'-modified nucleoside RT inhibitors.,Yasutake Y, Hattori SI, Tamura N, Matsuda K, Kohgo S, Maeda K, Mitsuya H Biochem Biophys Res Commun. 2019 Feb 19;509(4):943-948. doi:, 10.1016/j.bbrc.2019.01.026. Epub 2019 Jan 14. PMID:30648556<ref>PMID:30648556</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ika" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Hattori SI]]
[[Category: Maeda K]]
[[Category: Tamura N]]
[[Category: Yasutake Y]]