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5f6w

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Current revision

Crystal structure of Ubc9 (K48/K49A/E54A) complexed with Fragment 1 (biphenol)

Structural highlights

5f6w is a 1 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 1.699Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBC9_HUMAN Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is an important disease-associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray crystallographic screen was used to identify two distinct small-molecule fragments that bind to Ubc9 at a site distal to its catalytic cysteine. These fragments and related compounds inhibit SUMO conjugation in biochemical assays with potencies of 1.9-5.8 mm. Mechanistic and biophysical analyses, coupled with molecular dynamics simulations, point toward ligand-induced rigidification of Ubc9 as a mechanism of inhibition.

Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9.,Hewitt WM, Lountos GT, Zlotkowski K, Dahlhauser SD, Saunders LB, Needle D, Tropea JE, Zhan C, Wei G, Ma B, Nussinov R, Waugh DS, Schneekloth JS Jr Angew Chem Int Ed Engl. 2016 May 4;55(19):5703-7. doi: 10.1002/anie.201511351., Epub 2016 Apr 1. PMID:27038327^[8]

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

References

↑ Yasugi T, Howley PM. Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res. 1996 Jun 1;24(11):2005-10. PMID:8668529
↑ Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. PMID:11451954 doi:10.1074/jbc.M104214200
↑ Kim YE, Kim DY, Lee JM, Kim ST, Han TH, Ahn JH. Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for localization, sumoylation, and inhibition of monocyte differentiation. Biochem Biophys Res Commun. 2005 May 13;330(3):746-54. PMID:15809060 doi:10.1016/j.bbrc.2005.03.052
↑ Kuo FT, Bentsi-Barnes IK, Barlow GM, Bae J, Pisarska MD. Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene. Cell Signal. 2009 Dec;21(12):1935-44. doi: 10.1016/j.cellsig.2009.09.001. Epub, 2009 Sep 8. PMID:19744555 doi:10.1016/j.cellsig.2009.09.001
↑ Figueroa-Romero C, Iniguez-Lluhi JA, Stadler J, Chang CR, Arnoult D, Keller PJ, Hong Y, Blackstone C, Feldman EL. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 2009 Nov;23(11):3917-27. doi: 10.1096/fj.09-136630. Epub 2009 Jul 28. PMID:19638400 doi:10.1096/fj.09-136630
↑ Capili AD, Lima CD. Structure and analysis of a complex between SUMO and Ubc9 illustrates features of a conserved E2-Ubl interaction. J Mol Biol. 2007 Jun 8;369(3):608-18. Epub 2007 Apr 6. PMID:17466333 doi:10.1016/j.jmb.2007.04.006
↑ Sekiyama N, Arita K, Ikeda Y, Hashiguchi K, Ariyoshi M, Tochio H, Saitoh H, Shirakawa M. Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45. Proteins. 2009 Dec 4. PMID:20077568 doi:10.1002/prot.22667
↑ Hewitt WM, Lountos GT, Zlotkowski K, Dahlhauser SD, Saunders LB, Needle D, Tropea JE, Zhan C, Wei G, Ma B, Nussinov R, Waugh DS, Schneekloth JS Jr. Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9. Angew Chem Int Ed Engl. 2016 May 4;55(19):5703-7. doi: 10.1002/anie.201511351., Epub 2016 Apr 1. PMID:27038327 doi:http://dx.doi.org/10.1002/anie.201511351

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/5f6w"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Ubc9 (K48/K49A/E54A) complexed with Fragment 1 (biphenol)==
-<StructureSection load='5f6w' size='340' side='right' caption='[[5f6w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='5f6w' size='340' side='right'caption='[[5f6w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5f6w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F6W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5f6w]] is a 1 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=5F6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F6W FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5VL:2-(2-HYDROXYPHENYL)PHENOL'>5VL</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]] 1.699&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f6d|5f6d]], [[5f6e|5f6e]], [[5f6u|5f6u]], [[5f6v|5f6v]], [[5f6x|5f6x]], [[5f6y|5f6y]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5VL:2-(2-HYDROXYPHENYL)PHENOL'>5VL</scene></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=5f6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f6w OCA], [http://pdbe.org/5f6w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f6w RCSB], [http://www.ebi.ac.uk/pdbsum/5f6w PDBsum]</span></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=5f6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f6w OCA], [https://pdbe.org/5f6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f6w RCSB], [https://www.ebi.ac.uk/pdbsum/5f6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f6w ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/UBC9_HUMAN UBC9_HUMAN]] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.<ref>PMID:8668529</ref> <ref>PMID:11451954</ref> <ref>PMID:15809060</ref> <ref>PMID:19744555</ref> <ref>PMID:19638400</ref> <ref>PMID:17466333</ref> <ref>PMID:20077568</ref>
+[https://www.uniprot.org/uniprot/UBC9_HUMAN UBC9_HUMAN] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.<ref>PMID:8668529</ref> <ref>PMID:11451954</ref> <ref>PMID:15809060</ref> <ref>PMID:19744555</ref> <ref>PMID:19638400</ref> <ref>PMID:17466333</ref> <ref>PMID:20077568</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5f6w" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[SUMO conjugating enzyme Ubc9|SUMO conjugating enzyme Ubc9]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Dahlhauser, S]]
+[[Category: Homo sapiens]]
-[[Category: Hewitt, W M]]
+[[Category: Large Structures]]
-[[Category: Lountos, G T]]
+[[Category: Dahlhauser S]]
-[[Category: Ma, B]]
+[[Category: Hewitt WM]]
-[[Category: Needle, D]]
+[[Category: Lountos GT]]
-[[Category: Nussinov, R]]
+[[Category: Ma B]]
-[[Category: Saunders, L B]]
+[[Category: Needle D]]
-[[Category: Schneekloth, J S.Jr]]
+[[Category: Nussinov R]]
-[[Category: Tropea, J E]]
+[[Category: Saunders LB]]
-[[Category: Waugh, D S]]
+[[Category: Schneekloth JSJr]]
-[[Category: Wei, G]]
+[[Category: Tropea JE]]
-[[Category: Zhan, C]]
+[[Category: Waugh DS]]
-[[Category: Zlotkowski, K]]
+[[Category: Wei G]]
-[[Category: Fragment drug design]]
+[[Category: Zhan C]]
-[[Category: Ligase-ligase inhibitor complex]]
+[[Category: Zlotkowski K]]
-[[Category: Sumoylation]]
-[[Category: Ubc9]]

5f6w

From Proteopedia

Current revision

Crystal structure of Ubc9 (K48/K49A/E54A) complexed with Fragment 1 (biphenol)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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