期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 38, 期 -, 页码 1378-1385出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST0381378
关键词
cancer; hyaluronan; UDP-glucose dehydrogenase; UDP-glucuronic acid
资金
- Austrian Science Fund (DK Molecular Enzymology) [W901-B05]
- Austrian Science Fund (FWF) [W 901] Funding Source: researchfish
Biosynthesis of the glycosaminoglycan precursor UDP-alpha-D-glucuronic acid occurs through a 2-fold oxidation of UDP-alpha-D-glucose that is catalysed by UGDH (UDP-alpha-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 V-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 glycosanninoglycan formation is implicated in a variety of human diseases, including the progression of tumours. The inhibition of synthesis of UDP-alpha-D-glucuronic acid using UGDH antagonists might therefore be a useful strategy for therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据