The canonical kinase (ThiD) that converts the thiamin biosynthesis intermediate hydroxymethylpyrimidine (HMP) monophosphate into the diphosphate can also very efficiently convert free HMP into the monophosphate in prokaryotes, plants, and fungi. This HMP kinase activity enables salvage of HMP, but it is not substrate-specific and so allows toxic HMP analogs and damage products to infiltrate the thiamin biosynthesis pathway. Comparative analysis of bacterial genomes uncovered a gene, thiD2, that is often fused to the thiamin synthesis gene thiE and could potentially encode a replacement for ThiD. Standalone ThiD2 proteins and ThiD2 fusion domains are small (∼130 residues) and do not belong to any previously known protein family. Genetic and biochemical analyses showed that representative standalone and fused ThiD2 proteins catalyze phosphorylation of HMP monophosphate, but not of HMP or its toxic analogs and damage products such as bacimethrin and 5-(hydroxymethyl)-2-methylpyrimidin-4-ol. As strictly monofunctional HMP monophosphate kinases, ThiD2 proteins eliminate a potentially fatal vulnerability of canonical ThiD, at the cost of the ability to reclaim HMP formed by thiamin turnover.
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The distribution of haemagglutinin (green) and β-catenin (red) in MDCK cells overexpressing Akt1-HA. In this issue of the Biochemical Journal, Castañeda et al. report on the suppression of Akt/β-catenin-mediated cell proliferation by the the inhibition of 14-3-3ζ expression (see pages 2679–2689).
Research Article|
August 10 2017
A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis
Antje M. Thamm;
Antje M. Thamm
1Horticultural Sciences Department, University of Florida, Gainesville, FL, U.S.A.
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Gengnan Li;
Gengnan Li
2Department of Chemistry, University of Florida, Gainesville, FL, U.S.A.
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Marlene Taja-Moreno;
Marlene Taja-Moreno
1Horticultural Sciences Department, University of Florida, Gainesville, FL, U.S.A.
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Svetlana Y. Gerdes;
Svetlana Y. Gerdes
3Fellowship for Interpretation of Genomes, Burr Ridge, IL, U.S.A.
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Valérie de Crécy-Lagard;
Valérie de Crécy-Lagard
4Microbiology and Cell Science Department, University of Florida, Gainesville, FL 32611, U.S.A.
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Steven D. Bruner;
Steven D. Bruner
2Department of Chemistry, University of Florida, Gainesville, FL, U.S.A.
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Andrew D. Hanson
1Horticultural Sciences Department, University of Florida, Gainesville, FL, U.S.A.
Correspondence: Andrew D. Hanson (adha@ufl.edu)
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Publisher: Portland Press Ltd
Received:
June 02 2017
Revision Received:
July 17 2017
Accepted:
July 19 2017
Accepted Manuscript online:
July 20 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (16): 2887–2895.
Article history
Received:
June 02 2017
Revision Received:
July 17 2017
Accepted:
July 19 2017
Accepted Manuscript online:
July 20 2017
Citation
Antje M. Thamm, Gengnan Li, Marlene Taja-Moreno, Svetlana Y. Gerdes, Valérie de Crécy-Lagard, Steven D. Bruner, Andrew D. Hanson; A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis. Biochem J 15 August 2017; 474 (16): 2887–2895. doi: https://doi.org/10.1042/BCJ20170437
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