Publication Date:
2011-10-28
Description:
Thiamine pyrophosphate 1 is an essential cofactor in all living systems. Its biosynthesis involves the separate syntheses of the pyrimidine 2 and thiazole 3 precursors, which are then coupled. Two biosynthetic routes to the thiamine thiazole have been identified. In prokaryotes, five enzymes act on three substrates to produce the thiazole via a complex oxidative condensation reaction, the mechanistic details of which are now well established. In contrast, only one gene product is involved in thiazole biosynthesis in eukaryotes (THI4p in Saccharomyces cerevisiae). Here we report the preparation of fully active recombinant wild-type THI4p, the identification of an iron-dependent sulphide transfer reaction from a conserved cysteine residue of the protein to a reaction intermediate and the demonstration that THI4p is a suicide enzyme undergoing only a single turnover.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205460/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205460/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chatterjee, Abhishek -- Abeydeera, N Dinuka -- Bale, Shridhar -- Pai, Pei-Jing -- Dorrestein, Pieter C -- Russell, David H -- Ealick, Steven E -- Begley, Tadhg P -- DK44083/DK/NIDDK NIH HHS/ -- DK67081/DK/NIDDK NIH HHS/ -- R01 DK067081/DK/NIDDK NIH HHS/ -- R37 DK044083/DK/NIDDK NIH HHS/ -- R37 DK044083-21/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Oct 26;478(7370):542-6. doi: 10.1038/nature10503.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22031445" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
*Biocatalysis
;
Carbon-Nitrogen Lyases/chemistry/*metabolism
;
Conserved Sequence
;
Cysteine/metabolism
;
Iron/metabolism
;
Molecular Sequence Data
;
Recombinant Proteins
;
Saccharomyces cerevisiae/*enzymology
;
Saccharomyces cerevisiae Proteins/chemistry/*metabolism
;
Sulfides/metabolism
;
Sulfur/metabolism
;
Thiamine/*metabolism
;
Thiamine Pyrophosphate/metabolism
;
Thiazoles/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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