X-ray crystallography reveals a reduced substrate complex of UDP-galactopyranose mutase poised for covalent catalysis by flavin.

X-ray crystallography reveals a reduced substrate complex of UDP-galactopyranose mutase poised for covalent catalysis by flavin.
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X射线晶体学揭示了黄素有益于共价催化的UDP-半乳吡喃糖突变酶的底物复合物减少。

DOI:
10.1021/bi901437v
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发表时间:
2009-10-06
期刊:
影响因子:
2.9
通讯作者:
Forest, Katrina T.
Forest, Katrina T.
中科院分区:
生物学3区
文献类型:
--
作者:
Gruber, Todd D.;Westler, William M.;Kiessling, Laura L.;Forest, Katrina T.

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The flavoenzyme uridine 5’-diphosphate galactopyranose mutase (UGM or Glf) catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose. The latter is a key building block for cell wall construction in numerous pathogens, including Mycobacterium tuberculosis. Mechanistic studies of UGM suggested a novel role for the flavin, and we previously provided evidence that the catalytic mechanism proceeds through a covalent flavin-galactose iminium. Here, we describe 2.3 and 2.5 Å resolution X-ray crystal structures of the substrate-bound enzyme in oxidized and reduced forms, respectively. In the latter, the substrate C1 is 3.6 Å from the nucleophilic flavin N5 position. This orientation is consistent with covalent catalysis by flavin.
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