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4onm

From Proteopedia

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Crystal structure of human Mms2/Ubc13 - NSC697923

Structural highlights

4onm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.35Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-kappaB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-kappaB signaling in human cells. NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent adduct formation through a Michael addition at the Ubc13 active site cysteine. The resulting adducts of both compounds exploit a binding groove unique to Ubc13. We developed a Ubc13 mutant which resists NSC697923 inhibition and, using this mutant, we show that the inhibition of cellular DNA damage and NF-kappaB signaling by NSC697923 is largely due to specific Ubc13 inhibition. We propose that unique structural features near the Ubc13 active site could provide a basis for the rational development and design of specific Ubc13 inhibitors.

Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.,Hodge CD, Edwards RA, Markin CJ, McDonald D, Pulvino M, Huen MS, Zhao J, Spyracopoulos L, Hendzel MJ, Glover JN ACS Chem Biol. 2015 May 1. PMID:25909880^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xiao W, Lin SL, Broomfield S, Chow BL, Wei YF. The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family. Nucleic Acids Res. 1998 Sep 1;26(17):3908-14. PMID:9705497
↑ Hofmann RM, Pickart CM. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell. 1999 Mar 5;96(5):645-53. PMID:10089880
↑ Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene. 2003 Oct 16;22(46):7101-7. PMID:14562038 doi:10.1038/sj.onc.1206831
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Hodge CD, Edwards RA, Markin CJ, McDonald D, Pulvino M, Huen MS, Zhao J, Spyracopoulos L, Hendzel MJ, Glover JN. Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting. ACS Chem Biol. 2015 May 1. PMID:25909880 doi:http://dx.doi.org/10.1021/acschembio.5b00222

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4onm"

Categories: Homo sapiens | Large Structures | Edwards RA | Glover JNM | Hodge CD

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4onm]] 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=4ONM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ONM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=N2F:2-[(4-METHYLPHENYL)SULFONYL]-5-NITROFURAN'>N2F</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.35&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=N2F:2-[(4-METHYLPHENYL)SULFONYL]-5-NITROFURAN'>N2F</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=4onm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4onm OCA], [https://pdbe.org/4onm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4onm RCSB], [https://www.ebi.ac.uk/pdbsum/4onm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4onm ProSAT]</span></td></tr>
 </table>

4onm

From Proteopedia

Current revision

Crystal structure of human Mms2/Ubc13 - NSC697923

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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