Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily

被引：120

作者：

Chatterjee, Abhishek ^{[1
]}

Li, Yue ^{[1
]}

Zhang, Yang ^{[1
]}

Grove, Tyler L. ^{[2
]}

Lee, Michael ^{[3
]}

Krebs, Carsten ^{[2
,3
]}

Booker, Squire J. ^{[2
,3
]}

Begley, Tadhg P. ^{[1
]}

Ealick, Steven E. ^{[1
]}

机构：

[1] Cornell Univ, Baker Lab 120, Dept Chem & Biol Chem, Ithaca, NY 14853 USA

[2] Penn State Univ, Dept Chem, University Pk, PA 16802 USA

[3] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

来源：

NATURE CHEMICAL BIOLOGY | 2008年 / 4卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/nchembio.121

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase catalyzes a complex rearrangement of 5-aminoimidazole ribonucleotide (AIR) to form HMP-P, the pyrimidine moiety of thiamine phosphate. We determined the three-dimensional structures of HMP-P synthase and its complexes with the product HMP-P and a substrate analog imidazole ribotide. The structure of HMP-P synthase reveals a homodimer in which each protomer comprises three domains: an N-terminal domain with a novel fold, a central (beta alpha)(8) barrel and a disordered C-terminal domain that contains a conserved CX2CX4C motif, which is suggestive of a [4Fe-4S] cluster. Biochemical studies have confirmed that HMP-P synthase is iron sulfur cluster-dependent, that it is a new member of the radical SAM superfamily and that HMP-P and 5'-deoxyadenosine are products of the reaction. Mossbauer and EPR spectroscopy confirm the presence of one [4Fe-4S] cluster. Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies.

引用

页码：758 / 765

页数：8

共 47 条

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