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4y4l

From Proteopedia

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Crystal structure of yeast Thi4-C205S

Structural highlights

4y4l is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
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]

Publication Abstract from PubMed

Thiamin diphosphate is an essential cofactor in all forms of life and plays a key role in amino acid and carbohydrate metabolism. Its biosynthesis involves separate syntheses of the pyrimidine and thiazole moieties, which are then coupled to form thiamin monophosphate. A final phosphorylation produces the active form of the cofactor. In most bacteria, six gene products are required for biosynthesis of the thiamin thiazole. In yeast and fungi only one gene product, Thi4, is required for thiazole biosynthesis. Methanococcus jannaschii expresses a putative Thi4 ortholog that was previously reported to be a ribulose 1, 5-bisphosphate synthase [Finn, M. W. and Tabita, F. R. (2004) J. Bacteriol. 186, 6360-6366]. Our structural studies show that the Thi4 orthologs from M. jannaschii and Methanococcus igneus are structurally homologous to Thi4 from Saccharomyces cerevisiae . In addition, all active site residues are conserved except for a key cysteine residue, which in S. cerevisiae is the source of the thiazole sulfur atom. Our recent biochemical studies showed that the archael Thi4 orthologs use nicotinamide adenine dinucleotide, glycine and free sulfide to form the thiamin thiazole in an iron-dependent reaction [Eser, B., Zhang, X., Chanani, P. K., Ealick, S.E., and Begley, T.P. (2015) submitted]. Here we report X-ray crystal structures of Thi4 from M. jannaschii complexed with ADP-ribulose, the C205S variant of Thi4 from S. cerevisiae with a bound glycine imine intermediate, and Thi4 from M. igneus with bound glycine imine intermediate and iron. These studies reveal the structural basis for the iron-dependent mechanism of sulfur transfer in archael and yeast thiazole synthases.

Structural Basis for Iron-mediated Sulfur Transfer in Archael and Yeast Thiazole Synthases.,Zhang X, Eser BE, Chanani PK, Begley TP, Ealick SE Biochemistry. 2016 Feb 26. PMID:26919468^[8]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Zhang X, Eser BE, Chanani PK, Begley TP, Ealick SE. Structural Basis for Iron-mediated Sulfur Transfer in Archael and Yeast Thiazole Synthases. Biochemistry. 2016 Feb 26. PMID:26919468 doi:http://dx.doi.org/10.1021/acs.biochem.6b00030

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4y4l"

Categories: Large Structures | Saccharomyces cerevisiae S288C | Ealick SE | Zhang X

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4y4l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y4L FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=48N:(2E)-2-[(2S,4R)-5-[[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]OXY-OXIDANYL-PHOSPHORYL]OXY-4-OXIDANYL-3-OXIDANYLIDENE-PENTAN-2-YL]IMINOETHANOIC+ACID'>48N</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=48N:(2E)-2-[(2S,4R)-5-[[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]OXY-OXIDANYL-PHOSPHORYL]OXY-4-OXIDANYL-3-OXIDANYLIDENE-PENTAN-2-YL]IMINOETHANOIC+ACID'>48N</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4y4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y4l OCA], [https://pdbe.org/4y4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y4l RCSB], [https://www.ebi.ac.uk/pdbsum/4y4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y4l ProSAT]</span></td></tr>
 </table>

4y4l

From Proteopedia

Current revision

Crystal structure of yeast Thi4-C205S

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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