2q3e

From Proteopedia

(Difference between revisions)

Current revision

Structure of human UDP-glucose dehydrogenase complexed with NADH and UDP-glucose

Structural highlights

2q3e is a 12 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 2Å
Ligands:	, ,
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 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2q3e"

@@ Line 3: / Line 3: @@
 <StructureSection load='2q3e' size='340' side='right'caption='[[2q3e]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2q3e]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q3E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2q3e]] is a 12 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=2Q3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q3E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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]] 2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGDH ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2q3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3e OCA], [https://pdbe.org/2q3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q3e RCSB], [https://www.ebi.ac.uk/pdbsum/2q3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q3e ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
+[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: UDP-glucose 6-dehydrogenase]]
+[[Category: Arrowsmith C]]
-[[Category: Arrowsmith, C]]
+[[Category: Berridge G]]
-[[Category: Berridge, G]]
+[[Category: Bhatia C]]
-[[Category: Bhatia, C]]
+[[Category: Bunkoczi G]]
-[[Category: Bunkoczi, G]]
+[[Category: Edwards A]]
-[[Category: Delft, F von]]
+[[Category: Guo K]]
-[[Category: Edwards, A]]
+[[Category: Kavanagh KL]]
-[[Category: Guo, K]]
+[[Category: Oppermann U]]
-[[Category: Kavanagh, K L]]
+[[Category: Pilka E]]
-[[Category: Oppermann, U]]
+[[Category: Savitsky P]]
-[[Category: Pilka, E]]
+[[Category: Smee C]]
-[[Category: Structural genomic]]
+[[Category: Sundstrom M]]
-[[Category: Savitsky, P]]
+[[Category: Wiegelt J]]
-[[Category: Smee, C]]
+[[Category: Von Delft F]]
-[[Category: Sundstrom, M]]
-[[Category: Wiegelt, J]]
-[[Category: Hexamer]]
-[[Category: Oxidoreductase]]
-[[Category: Sgc]]
-[[Category: Udp-glucose 6-dehydrogenase]]

2q3e

From Proteopedia

Current revision

Structure of human UDP-glucose dehydrogenase complexed with NADH and UDP-glucose

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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