View source for 4nrg


==Crystal Structure of a human Mms2/Ubc13 D118G mutant==
<StructureSection load='4nrg' size='340' side='right'caption='[[4nrg]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nrg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NRG 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]] 1.95&#8491;</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=4nrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nrg OCA], [https://pdbe.org/4nrg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nrg RCSB], [https://www.ebi.ac.uk/pdbsum/4nrg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nrg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UB2V2_HUMAN UB2V2_HUMAN] Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.<ref>PMID:9705497</ref> <ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:20061386</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Initiation of the DNA damage and innate immune responses is dependent upon the flow of chemical information through coupled protein-protein interaction networks and driven by the synthesis and recognition of Lys 63 linked polyubiquitin (polyUb) chains on adaptor proteins. The central chemical step in Lys 63-linked protein ubiquitination involves the reaction of a specific lysine on a target protein with Ub that is covalently attached as a thioester conjugate to the Ub conjugating enzyme (E2) Ubc13. The active site cysteine of Ubc13, and E2 enzymes in general, is buttressed by a flexible loop. The role of loop dynamics in catalysis was investigated by mutating the central and hinge residues to glycine. The loop dynamics were experimentally characterized through measurement of enzyme kinetics, main chain NMR relaxation, X-ray crystallographic studies, and in vivo studies in yeast. The experimental data were complemented by analysis of MD simulations of the dynamics and kinetics for the loop motion. The results show that fast pico- to nanosecond time scale active site loop fluctuations play a crucial role in regulating the catalytic activity of Ubc13 by functioning as a stochastic active site gate, which is characterized by precisely balanced rates of opening and closing. In vivo functional complementation assays in yeast demonstrate that defects within this regulatory mechanism can have profound biological consequences, given that Ubc13 is the only E2 dedicated to synthesizing Lys 63-linked polyUb chains.

Stochastic Gate Dynamics Regulate the Catalytic Activity of Ubiquitination Enzymes.,Rout MK, Hodge CD, Markin CJ, Xu X, Glover JN, Xiao W, Spyracopoulos L J Am Chem Soc. 2014 Dec 5. PMID:25423605<ref>PMID:25423605</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4nrg" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Edwards RA]]
[[Category: Glover JNM]]
[[Category: Hodge CD]]