|
CATH domain | Related DB codes (homologues) |
---|
3.20.20.70 : TIM Barrel | S00215,S00217,S00218,S00219,S00532,S00198,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089 |
Enzyme Name | UniProtKB | KEGG |
---|
| P39594 |
---|
Protein name | Thiamine-phosphate pyrophosphorylase | thiamine-phosphate diphosphorylasethiamine phosphate pyrophosphorylasethiamine monophosphate pyrophosphorylaseTMP-PPase |
---|
Synonyms | TMP pyrophosphorylaseTMP-PPaseEC 2.5.1.3Thiamine-phosphate synthase |
---|
RefSeq | NP_391708.1 (Protein) NC_000964.3 (DNA/RNA sequence)
|
---|
Pfam | PF02581 (TMP-TENI) [Graphical view]
|
---|
KEGG pathways | MAP code | Pathways |
---|
MAP00730 | Thiamine metabolism |
UniProtKB:Accession Number | P39594 |
---|
Entry name | THIE_BACSU |
---|
Activity | 2-methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 4-methyl-5-(2-phosphono-oxyethyl)thiazole = diphosphate + thiamine phosphate. |
---|
Subunit | Monomer. |
---|
Subcellular location |
|
---|
Cofactor | Binds 1 magnesium ion per subunit. |
---|
Compound table: links to PDB-related databases & PoSSuM |
---|
| Cofactors | Substrates | Products | intermediates |
---|
KEGG-id | C00305 | C04752 | C04327 | C00013 | C01081 |
|
---|
Compound | Magnesium | 2-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate | 4-Methyl-5-(2-phosphono-oxyethyl)-thiazole | Diphosphate | Thiamin monophosphate |
|
---|
Type | divalent metal (Ca2+, Mg2+) | amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion | aromatic ring (with nitrogen atoms),phosphate group/phosphate ion | phosphate group/phosphate ion | amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion |
|
---|
ChEBI | 18420
| 16629
| 17857
| 29888
| 9533
|
|
---|
PubChem | 888
| 217
| 1137
| 21961011 1023
| 1131
|
|
---|
| | | | | | | | | | | | | |
---|
1g4eA |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1g4eB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1g4pA |  |  |  |  |  |  |  | Bound:_MG | Analogue:FQP | Unbound | Unbound | Unbound | Unbound |
---|
1g4pB |  |  |  |  |  |  |  | Bound:_MG | Analogue:FQP | Unbound | Unbound | Unbound | Unbound |
---|
1g4sA |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Bound:TPS | Unbound |
---|
1g4sB |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Bound:TPS | Unbound |
---|
1g4tA |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Analogue:FTP | Unbound |
---|
1g4tB |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Analogue:FTP | Unbound |
---|
1g67A |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-bound:ICP |
---|
1g67B |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-bound:ICP |
---|
1g69A |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-bound:ICP |
---|
1g69B |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-bound:ICP |
---|
1g6cA |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-analogue:IFP |
---|
1g6cB |  |  |  |  |  |  |  | Bound:_MG | Unbound | Bound:TZP | Bound:POP | Unbound | Intermediate-analogue:IFP |
---|
2tpsA |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Bound:TPS | Unbound |
---|
2tpsB |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Bound:POP | Bound:TPS | Unbound |
---|
References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
---|
[2] | p.298 |
| [3] | Fig.8, p.6468 |
| [5] | Scheme 2, p.10111 |
| [6] | FIGURE 2, p.10096 |
| [6] | FIGURE 14, p.10101 |
|
references | [1] |
---|
Comments | CHARACTERIZATION. |
---|
Medline ID | 97284509 |
---|
PubMed ID | 9139923 |
---|
Journal | J Bacteriol |
---|
Year | 1997 |
---|
Volume | 179 |
---|
Pages | 3030-5 |
---|
Authors | Zhang Y, Taylor SV, Chiu HJ, Begley TP |
---|
Title | Characterization of the Bacillus subtilis thiC operon involved in thiamine biosynthesis |
---|
Related UniProtKB | P39594 |
---|
[2] |
---|
PubMed ID | 10382260 |
---|
Journal | Arch Microbiol |
---|
Year | 1999 |
---|
Volume | 171 |
---|
Pages | 293-300 |
---|
Authors | Begley TP, Downs DM, Ealick SE, McLafferty FW, Van Loon AP, Taylor S, Campobasso N, Chiu HJ, Kinsland C, Reddick JJ, Xi J |
---|
Title | Thiamin biosynthesis in prokaryotes. |
---|
[3] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS). |
---|
Medline ID | 99280703 |
---|
PubMed ID | 10350464 |
---|
Journal | Biochemistry |
---|
Year | 1999 |
---|
Volume | 38 |
---|
Pages | 6460-70 |
---|
Authors | Chiu HJ, Reddick JJ, Begley TP, Ealick SE |
---|
Title | Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolution |
---|
Related PDB | 2tps |
---|
Related UniProtKB | P39594 |
---|
[4] |
---|
PubMed ID | 11054297 |
---|
Journal | J Mol Biol |
---|
Year | 2000 |
---|
Volume | 303 |
---|
Pages | 627-41 |
---|
Authors | Copley RR, Bork P |
---|
Title | Homology among (betaalpha)(8) barrels: implications for the evolution of metabolic pathways. |
---|
[5] |
---|
Comments | X-ray crystallography |
---|
PubMed ID | 11513589 |
---|
Journal | Biochemistry |
---|
Year | 2001 |
---|
Volume | 40 |
---|
Pages | 10103-14 |
---|
Authors | Peapus DH, Chiu HJ, Campobasso N, Reddick JJ, Begley TP, Ealick SE |
---|
Title | Structural characterization of the enzyme-substrate, enzyme-intermediate, and enzyme-product complexes of thiamin phosphate synthase. |
---|
Related PDB | 1g4e,1g4p,1g4s,1g4t,1g67,1g69,1g6c |
---|
[6] |
---|
PubMed ID | 11513588 |
---|
Journal | Biochemistry |
---|
Year | 2001 |
---|
Volume | 40 |
---|
Pages | 10095-102 |
---|
Authors | Reddick JJ, Nicewonger R, Begley TP |
---|
Title | Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative mechanism. |
---|
[7] |
---|
PubMed ID | 14675553 |
---|
Journal | Curr Opin Struct Biol |
---|
Year | 2003 |
---|
Volume | 13 |
---|
Pages | 739-47 |
---|
Authors | Settembre E, Begley TP, Ealick SE |
---|
Title | Structural biology of enzymes of the thiamin biosynthesis pathway. |
---|
comments | The literature [2] & [3] suggested that this enzyme catalyzes SN1-like transfer reaction, forming a carbenium intermediate. In contrast, the other literature [5] & [6] suggested that it catalyzes two successive reactions, (A) Elimination of pyrophosphate group, forming a double-bond at C7'-C5' of the first substrate (HMP-PP), and (B) Addition of thiazole group to the double-bond. According to the literature [5], despite the important role of Ser130 in catalysis, the mutant S130A does not prevent the first reaction, forming an intermediate. Thus, the residue must be involved more importantly in the second reaction. The reaction probably proceeds as follows (see [5] & [6]); (A) Eliminative double-bond formation: Elimination of phosphate group (A1) The eliminated group, pyrophosphate, is stabilized by magnesium ion, which is bound to Asp93 and Asp112, along with Arg59, Lys61, Ser130, and Lys159. The pyrimidine ring (of leaving group) is stabilized by Gln57. (A2) Bond cleavage between C7'-O5 (of alpha-phosphate) occurs first, forming a carbocation intermediate. (E1-like reaction) (A3) The beta-phosphate oxygen acts as a general base to deprotonate the N4' amine (deprotonation site) of the pyrimidine ring, leading to the formation of double bonds at C7'-C5' bond and C4'-N4' bond, forming an iminemethide intermediate. (B) Addition of thiazole group to the intermediate. (B1) During this reaction, Ser130 must modulate the interaction between the C7' of the pyrimidine ring and the eliminated pyrophosphate. The N4' imine of the pyrimidine ring (of unsaturated group) is stabilized by Gln57. (B2) The added group, the nitrogen atom of the thiazole group of the second substrate, makes a nucleophilic attack on the C7' atom of the iminemethide intermediate. (B3) The beta-phosphate oxygen acts as a general acid to protonate the N4' imine, in a concerted mode, to complete the reaction.
|
created | updated |
---|
2005-03-22 | 2009-02-26 |
|
|