Reconstitution of ThiC in Thiamine Pyrimidine Biosynthesis Expands the Radical SAM Superfamily

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2008 Oct 28

PMID 18953358

Citations 77

Authors

Abhishek Chatterjee

Yue Li

Yang Zhang

Tyler L Grove

Michael Lee

Carsten Krebs

Squire J Booker

Tadhg P Begley

Steven E Ealick

Affiliations

Soon will be listed here.

Abstract

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 (betaalpha)(8) barrel and a disordered C-terminal domain that contains a conserved CX(2)CX(4)C 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. Mössbauer 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.

Citing Articles

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