5dzm: Difference between revisions
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New page: '''Unreleased structure''' The entry 5dzm is ON HOLD Authors: Pedersen, L.C., London, R.E., Gabel, S.A., Zheng, X.H. Description: Category: Unreleased Structures [[Category: Zheng... |
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==HIV-1 Reverse Transcriptase RH domain== | |||
<StructureSection load='5dzm' size='340' side='right'caption='[[5dzm]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dzm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DZM 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]] 2.05Å</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=5dzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dzm OCA], [https://pdbe.org/5dzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dzm RCSB], [https://www.ebi.ac.uk/pdbsum/5dzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dzm ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7LYY8_9HIV1 Q7LYY8_9HIV1] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. This study demonstrates the feasibility of directly targeting RT maturation with therapeutics. | |||
Unfolding the HIV-1 reverse transcriptase RNase H domain - how to lose a molecular tug-of-war.,Zheng X, Pedersen LC, Gabel SA, Mueller GA, DeRose EF, London RE Nucleic Acids Res. 2016 Feb 29;44(4):1776-88. doi: 10.1093/nar/gkv1538. Epub 2016, Jan 14. PMID:26773054<ref>PMID:26773054</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5dzm" style="background-color:#fffaf0;"></div> | ||
[[Category: Gabel | |||
[[Category: London | ==See Also== | ||
[[Category: Pedersen | *[[Reverse transcriptase 3D structures|Reverse transcriptase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human immunodeficiency virus 1]] | |||
[[Category: Large Structures]] | |||
[[Category: Gabel SA]] | |||
[[Category: London RE]] | |||
[[Category: Pedersen LC]] | |||
[[Category: Zheng XH]] | |||