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2qg4

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Revision as of 09:46, 18 October 2017

Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate

Structural highlights

2qg4 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	2q3e
Gene:	UGDH (HUMAN)
Activity:	UDP-glucose 6-dehydrogenase, with EC number 1.1.1.22
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UGDH_HUMAN] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Elevated production of the matrix glycosaminoglycan hyaluronan is strongly implicated in epithelial tumor progression. Inhibition of synthesis of the hyaluronan precursor UDP-glucuronic acid (UDP-GlcUA) therefore presents an emerging target for cancer therapy. Human UDP-glucose 6-dehydrogenase (hUGDH) catalyzes, in two NAD(+)-dependent steps without release of intermediate aldehyde, the biosynthetic oxidation of UDP-glucose (UDP-Glc) to UDP-GlcUA. Here, we present a structural characterization of the hUGDH reaction coordinate using crystal structures of the apoenzyme and ternary complexes of the enzyme bound with UDP-Glc/NADH and UDP-GlcUA/NAD(+). The quaternary structure of hUGDH is a disc-shaped trimer of homodimers whose subunits consist of two discrete alpha/beta domains with the active site located in the interdomain cleft. Ternary complex formation is accompanied by rigid-body and restrained movement of the N-terminal NAD(+) binding domain, sequestering substrate and coenzyme in their reactive positions through interdomain closure. By alternating between conformations in and out of the active site during domain motion, Tyr(14), Glu(161), and Glu(165) participate in control of coenzyme binding and release during 2-fold oxidation. The proposed mechanism of hUGDH involves formation and breakdown of thiohemiacetal and thioester intermediates whereby Cys(276) functions as the catalytic nucleophile. Stopped-flow kinetic data capture the essential deprotonation of Cys(276) in the course of the first oxidation step, allowing the thiolate side chain to act as a trap of the incipient aldehyde. Because thiohemiacetal intermediate accumulates at steady state under physiological reaction conditions, hUGDH inhibition might best explore ligand binding to the NAD(+) binding domain.

Structure and mechanism of human UDP-glucose 6-dehydrogenase.,Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B J Biol Chem. 2011 Jul 8;286(27):23877-87. Epub 2011 Apr 18. PMID:21502315^[1]

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

References

↑ Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B. Structure and mechanism of human UDP-glucose 6-dehydrogenase. J Biol Chem. 2011 Jul 8;286(27):23877-87. Epub 2011 Apr 18. PMID:21502315 doi:10.1074/jbc.M111.234682

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2qg4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate==
 <StructureSection load='2qg4' size='340' side='right' caption='[[2qg4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </span></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=2qg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qg4 OCA], [http://pdbe.org/2qg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qg4 RCSB], [http://www.ebi.ac.uk/pdbsum/2qg4 PDBsum]</span></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=2qg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qg4 OCA], [http://pdbe.org/2qg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qg4 RCSB], [http://www.ebi.ac.uk/pdbsum/2qg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qg4 ProSAT]</span></td></tr>
 </table>
 == Function ==

2qg4

From Proteopedia

Revision as of 09:46, 18 October 2017

Crystal structure of human UDP-glucose dehydrogenase product complex with UDP-glucuronate

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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