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Structural studies of thiamin monophosphate kinase in complex with substrates and products.

Authors
  • McCulloch, Kathryn M
  • Kinsland, Cynthia
  • Begley, Tadhg P
  • Ealick, Steven E
Type
Published Article
Journal
Biochemistry
Publication Date
Mar 25, 2008
Volume
47
Issue
12
Pages
3810–3821
Identifiers
DOI: 10.1021/bi800041h
PMID: 18311927
Source
Medline
License
Unknown

Abstract

Thiamin monophosphate kinase (ThiL) catalyzes the ATP-dependent phosphorylation of thiamin monophosphate (TMP) to form thiamin pyrophosphate (TPP), the active form of vitamin B 1. ThiL is a member of a small ATP binding superfamily that also includes the purine biosynthetic enzymes, PurM and PurL, NiFe hydrogenase maturation protein, HypE, and selenophosphate synthase, SelD. The latter four enzymes are believed to utilize phosphorylated intermediates during catalysis. To understand the mechanism of ThiL and its relationship to the other superfamily members, we determined the structure of Aquifex aeolicus ThiL (AaThiL) with nonhydrolyzable AMP-PCP and TMP, and also with the products of the reaction, ADP and TPP. The results suggest that AaThiL utilizes a direct, inline transfer of the gamma-phosphate of ATP to TMP rather than a phosphorylated enzyme intermediate. The structure of ThiL is compared to those of PurM, PurL, and HypE, and the ATP binding site is compared to that of PurL, for which nucleotide complexes are available.

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