Proteopedia

3fpz

Saccharomyces cerevisiae THI4p is a suicide thiamin thiazole synthaseSaccharomyces cerevisiae THI4p is a suicide thiamin thiazole synthase

Structural highlights

3fpz is a 2 chain structure with sequence from Saccharomyces cerevisiae. This structure supersedes the now removed PDB entry 2gjc. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.82Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THI4_YEAST Involved in biosynthesis of the thiamine precursor thiazole. Catalyzes the conversion of NAD and glycine to adenosine diphosphate 5-(2-hydroxyethyl)-4-methylthiazole-2-carboxylic acid (ADT), an adenylated thiazole intermediate. The reaction includes an iron-dependent sulfide transfer from a conserved cysteine residue of the protein to a thiazole intermediate. The enzyme can only undergo a single turnover, which suggests it is a suicide enzyme. May have additional roles in adaptation to various stress conditions and in DNA damage tolerance.[1] [2] [3] [4] [5] [6] [7]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase.,Chatterjee A, Abeydeera ND, Bale S, Pai PJ, Dorrestein PC, Russell DH, Ealick SE, Begley TP Nature. 2011 Oct 26;478(7370):542-6. doi: 10.1038/nature10503. PMID:22031445[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Faou P, Tropschug M. Neurospora crassa CyPBP37: a cytosolic stress protein that is able to replace yeast Thi4p function in the synthesis of vitamin B1. J Mol Biol. 2004 Dec 3;344(4):1147-57. PMID:15544818 doi:10.1016/j.jmb.2004.09.097
  2. ↑ Machado CR, Praekelt UM, de Oliveira RC, Barbosa AC, Byrne KL, Meacock PA, Menck CF. Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance. J Mol Biol. 1997 Oct 17;273(1):114-21. PMID:9367751 doi:http://dx.doi.org/S0022-2836(97)91302-4
  3. ↑ Chatterjee A, Jurgenson CT, Schroeder FC, Ealick SE, Begley TP. Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis. J Am Chem Soc. 2006 Jun 7;128(22):7158-9. PMID:16734458 doi:http://dx.doi.org/10.1021/ja061413o
  4. ↑ Medina-Silva R, Barros MP, Galhardo RS, Netto LE, Colepicolo P, Menck CF. Heat stress promotes mitochondrial instability and oxidative responses in yeast deficient in thiazole biosynthesis. Res Microbiol. 2006 Apr;157(3):275-81. Epub 2005 Aug 30. PMID:16171982 doi:http://dx.doi.org/10.1016/j.resmic.2005.07.004
  5. ↑ Chatterjee A, Jurgenson CT, Schroeder FC, Ealick SE, Begley TP. Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate. J Am Chem Soc. 2007 Mar 14;129(10):2914-22. Epub 2007 Feb 20. PMID:17309261 doi:http://dx.doi.org/10.1021/ja067606t
  6. ↑ Chatterjee A, Schroeder FC, Jurgenson CT, Ealick SE, Begley TP. Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a thiazole tautomer intermediate. J Am Chem Soc. 2008 Aug 27;130(34):11394-8. doi: 10.1021/ja802140a. Epub 2008 Jul, 25. PMID:18652458 doi:http://dx.doi.org/10.1021/ja802140a
  7. ↑ Chatterjee A, Abeydeera ND, Bale S, Pai PJ, Dorrestein PC, Russell DH, Ealick SE, Begley TP. Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase. Nature. 2011 Oct 26;478(7370):542-6. doi: 10.1038/nature10503. PMID:22031445 doi:10.1038/nature10503
  8. ↑ Chatterjee A, Abeydeera ND, Bale S, Pai PJ, Dorrestein PC, Russell DH, Ealick SE, Begley TP. Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase. Nature. 2011 Oct 26;478(7370):542-6. doi: 10.1038/nature10503. PMID:22031445 doi:10.1038/nature10503

3fpz, resolution 1.82Å

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