Biosynthesis of the glycosaminoglycan precursor UDP-α-D-glucuronic acid occurs through a 2-fold oxidation of UDP-α-D-glucose that is catalysed by UGDH (UDP-α-D-glucose 6-dehydrogenase). Structure–function relationships for UGDH and proposals for the enzymatic reaction mechanism are reviewed in the present paper, and structure-based sequence comparison is used for subclassification of UGDH family members. The eukaryotic group of enzymes (UGDH-II) utilize an extended C-terminal domain for the formation of complex homohexameric assemblies. The comparably simpler oligomerization behaviour of the prokaryotic group of enzymes (UGDH-I), in which dimeric forms prevail, is traced back to the lack of relevant intersubunit contacts and trimmings within the C-terminal region. The active site of UGDH contains a highly conserved cysteine residue, which plays a key role in covalent catalysis. Elevated glycosaminoglycan formation is implicated in a variety of human diseases, including the progression of tumours. The inhibition of synthesis of UDP-α-D-glucuronic acid using UGDH antagonists might therefore be a useful strategy for therapy.
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October 2010
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Conference Article|
September 24 2010
UDP-glucose dehydrogenase: structure and function of a potential drug target
Sigrid Egger;
Sigrid Egger
*Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, Petersgasse 12, A-8010 Graz, Austria
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Apirat Chaikuad;
Apirat Chaikuad
†Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, U.K.
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Kathryn L. Kavanagh;
Kathryn L. Kavanagh
†Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, U.K.
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Udo Oppermann;
Udo Oppermann
†Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, U.K.
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Bernd Nidetzky
Bernd Nidetzky
1
*Institute of Biotechnology and Biochemical Engineering, Graz University of Technology, Petersgasse 12, A-8010 Graz, Austria
1To whom correspondence should be addressed (email bernd.nidetzky@tugraz.at).
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Publisher: Portland Press Ltd
Received:
May 18 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (5): 1378–1385.
Article history
Received:
May 18 2010
Citation
Sigrid Egger, Apirat Chaikuad, Kathryn L. Kavanagh, Udo Oppermann, Bernd Nidetzky; UDP-glucose dehydrogenase: structure and function of a potential drug target. Biochem Soc Trans 1 October 2010; 38 (5): 1378–1385. doi: https://doi.org/10.1042/BST0381378
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