Enzymes
UniProtKB help_outline | 25,939 proteins |
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- Name help_outline 1-deoxy-D-xylulose 5-phosphate Identifier CHEBI:57792 (Beilstein: 11127452) help_outline Charge -2 Formula C5H9O7P InChIKeyhelp_outline AJPADPZSRRUGHI-RFZPGFLSSA-L SMILEShelp_outline CC(=O)[C@@H](O)[C@H](O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 8 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-iminoacetate Identifier CHEBI:77846 Charge 0 Formula C2H3NO2 InChIKeyhelp_outline TVMUHOAONWHJBV-UHFFFAOYSA-N SMILEShelp_outline [O-]C(=O)C=[NH2+] 2D coordinates Mol file for the small molecule Search links Involved in 5 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
[sulfur-carrier protein ThiS]-C-terminal Gly-NH-CH2-C(O)SH
Identifier
RHEA-COMP:12908
Reactive part
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- Name help_outline C-terminal Gly-NH-CH(2)-C(O)SH residue Identifier CHEBI:90619 Charge 0 Formula C4H7N2O2S SMILEShelp_outline SC(CNC(CN*)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 6 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate Identifier CHEBI:62899 Charge -3 Formula C7H7NO6PS InChIKeyhelp_outline PQMCQNOVNFNPFJ-HYIMLASBSA-K SMILEShelp_outline CC1=N[C@H](SC\1=C/COP([O-])([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
[sulfur-carrier protein ThiS]-C-terminal Gly-Gly
Identifier
RHEA-COMP:12909
Reactive part
help_outline
- Name help_outline C-terminal Gly-Gly residue Identifier CHEBI:90778 Charge -1 Formula C4H6N2O3 SMILEShelp_outline [O-]C(CNC(CN*)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 9 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:26297 | RHEA:26298 | RHEA:26299 | RHEA:26300 | |
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Publications
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The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS.
Dorrestein P.C., Zhai H., McLafferty F.W., Begley T.P.
Thiamin-pyrophosphate is an essential cofactor in all living systems. The biosynthesis of both the thiazole and the pyrimidine moieties of this cofactor involves new biosynthetic chemistry. Thiazole-phosphate synthase (ThiG) catalyses the formation of the thiazole moiety of thiamin-pyrophosphate f ... >> More
Thiamin-pyrophosphate is an essential cofactor in all living systems. The biosynthesis of both the thiazole and the pyrimidine moieties of this cofactor involves new biosynthetic chemistry. Thiazole-phosphate synthase (ThiG) catalyses the formation of the thiazole moiety of thiamin-pyrophosphate from 1-deoxy-D-xylulose-5-phosphate (DXP), dehydroglycine and the sulfur carrier protein (ThiS), modified on its carboxy terminus as a thiocarboxylate (ThiS-thiocarboxylate). Thiazole biosynthesis is initiated by the formation of a ThiG/DXP imine, which then tautomerizes to an amino-ketone. In this paper we study the sulfur transfer from ThiS-thiocarboxylate to this amino-ketone and trap a new thioenolate intermediate. Surprisingly, thiazole formation results in the replacement of the ThiS-thiocarboxylate sulfur with an oxygen from DXP and not from the buffer, as shown by electrospray ionization Fourier transform mass spectrometry (ESI-FTMS) using (18)O labeling of the 13C-, 15N-depleted protein. These observations further clarify the mechanism of the complex thiazole biosynthesis in bacteria. << Less
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Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reaction.
Hazra A., Chatterjee A., Begley T.P.
In this paper, we describe an optimized reconstitution of the thiamin thiazole synthase (ThiG) catalyzed reaction and demonstrate that the enzymatic product is an unanticipated dearomatized thiazole tautomer.
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Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B1).
Park J.-H., Dorrestein P.C., Zhai H., Kinsland C., McLafferty F.W., Begley T.P.
While most of the proteins required for the biosynthesis of thiamin pyrophosphate have been known for more than a decade, the reconstitution of this biosynthesis in a defined biochemical system has been difficult due to the novelty of the chemistry involved. Here we demonstrate the first successfu ... >> More
While most of the proteins required for the biosynthesis of thiamin pyrophosphate have been known for more than a decade, the reconstitution of this biosynthesis in a defined biochemical system has been difficult due to the novelty of the chemistry involved. Here we demonstrate the first successful enzymatic synthesis of the thiazole moiety of thiamin from glycine, cysteine, and deoxy-D-xylulose-5-phosphate using overexpressed Bacillus subtilis ThiF, ThiS, ThiO, ThiG, and a NifS-like protein. This has facilitated the identification of the biochemical function of each of the proteins involved: ThiF catalyzes the adenylation of ThiS; NifS catalyzes the transfer of sulfur from cysteine to the acyl adenylate of ThiS; ThiO catalyzes the oxidation of glycine to the corresponding imine; and ThiG catalyzes the formation of the thiazole phosphate ring. The complex oxidative cyclization reaction involved in the biosynthesis of the thiamin thiazole has been greatly simplified by replacing ThiF, ThiS, ThiO, and NifS with defined biosynthetic intermediates in a reaction where ThiG is the only required enzyme. << Less
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Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complex.
Settembre E.C., Dorrestein P.C., Zhai H., Chatterjee A., McLafferty F.W., Begley T.P., Ealick S.E.
Thiazole synthase is the key enzyme involved in the formation of the thiazole moiety of thiamin pyrophosphate. We have determined the structure of this enzyme in complex with ThiS, the sulfur carrier protein, at 3.15 A resolution. Thiazole synthase is a tetramer with 222 symmetry. The monomer is a ... >> More
Thiazole synthase is the key enzyme involved in the formation of the thiazole moiety of thiamin pyrophosphate. We have determined the structure of this enzyme in complex with ThiS, the sulfur carrier protein, at 3.15 A resolution. Thiazole synthase is a tetramer with 222 symmetry. The monomer is a (betaalpha)(8) barrel with similarities to the aldolase class 1 and flavin mononucleotide dependent oxidoreductase and phosphate binding superfamilies. The sulfur carrier protein (ThiS) is a compact protein with a fold similar to that of ubiquitin. The structure allowed us to model the substrate, deoxy-D-xylulose 5-phosphate (DXP), in the active site. This model identified Glu98 and Asp182 as new active site residues likely to be involved in the catalysis of thiazole formation. The function of these residues was probed by mutagenesis experiments, which confirmed that both residues are essential for thiazole formation and identified Asp182 as the base involved in the deprotonation at C3 of the thiazole synthase DXP imine. Comparison of the ThiS binding surface to the surface of ubiquitin identified a conserved hydrophobic patch of unknown function on ubiquitin that may be involved in complex formation between ubiquitin and one of its binding partners. << Less
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A missing enzyme in thiamin thiazole biosynthesis: identification of TenI as a thiazole tautomerase.
Hazra A.B., Han Y., Chatterjee A., Zhang Y., Lai R.Y., Ealick S.E., Begley T.P.
In many bacteria tenI is found clustered with genes involved in thiamin thiazole biosynthesis. However, while TenI shows high sequence similarity with thiamin phosphate synthase, the purified protein has no thiamin phosphate synthase activity, and the role of this enzyme in thiamin biosynthesis re ... >> More
In many bacteria tenI is found clustered with genes involved in thiamin thiazole biosynthesis. However, while TenI shows high sequence similarity with thiamin phosphate synthase, the purified protein has no thiamin phosphate synthase activity, and the role of this enzyme in thiamin biosynthesis remains unknown. In this contribution, we identify the function of TenI as a thiazole tautomerase, describe the structure of the enzyme complexed with its reaction product, identify the substrates phosphate and histidine 122 as the acid/base residues involved in catalysis, and propose a mechanism for the reaction. The identification of the function of TenI completes the identification of all of the enzymes needed for thiamin biosynthesis by the major bacterial pathway. << Less
J. Am. Chem. Soc. 133:9311-9319(2011) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B1): the early steps catalyzed by thiazole synthase.
Dorrestein P.C., Zhai H., Taylor S.V., McLafferty F.W., Begley T.P.
Thiazole synthase (ThiG) catalyzes an Amadori-type rearrangement of 1-deoxy-d-xylulose-5-phosphate (DXP) via an imine intermediate. In support of this, we have demonstrated enzyme-catalyzed exchange of the C2 carbonyl of DXP. Borohydride reduction of the enzyme DXP imine followed by top-down mass ... >> More
Thiazole synthase (ThiG) catalyzes an Amadori-type rearrangement of 1-deoxy-d-xylulose-5-phosphate (DXP) via an imine intermediate. In support of this, we have demonstrated enzyme-catalyzed exchange of the C2 carbonyl of DXP. Borohydride reduction of the enzyme DXP imine followed by top-down mass spectrometric analysis localized the imine to lysine 96. On the basis of these observations, a new mechanism for the biosynthesis of the thiazole phosphate moiety of thiamin pyrophosphate in Bacillus subtilis is proposed. This mechanism involves the generation of a ketone at C3 of DXP by an Amadori-type rearrangement of the imine followed by nucleophillic addition of the sulfur carrier protein (ThiS-thiocarboxylate) to this carbonyl group. << Less