P39594 (THIE_BACSU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiamine-phosphate synthase
Short name=TP synthase
Short name=TPS
EC=2.5.1.3

Alternative name(s):
Thiamine-phosphate pyrophosphorylase
Short name=TMP pyrophosphorylase
Short name=TMP-PPase

Gene names

Name:	thiE
Synonyms:	thiC, ywbK
Ordered Locus Names:	BSU38290
ORF Names:	ipa-26d

Organism

Bacillus subtilis (strain 168) [Reference proteome] [HAMAP]

Taxonomic identifier

224308 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Bacillaceae › Bacillus › Bacillus subtilis group › Bacillus subtilis › Bacillus subtilis subsp. subtilis

Protein attributes

Sequence length	222 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP). Is also able to use the 2-methoxy analog MeO-HMP-PP, as substrate in vitro, but not the 2-trifluoromethyl analog CF(3)-HMP-PP. Ref.3 Ref.4
Catalytic activity	2-methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 4-methyl-5-(2-phosphono-oxyethyl)thiazole = diphosphate + thiamine phosphate. Ref.3
Cofactor	Binds 1 magnesium ion per subunit. Ref.3
Pathway	Cofactor biosynthesis; thiamine diphosphate biosynthesis; thiamine phosphate from 4-amino-2-methyl-5-diphosphomethylpyrimidine and 4-methyl-5-(2-phosphoethyl)-thiazole: step 1/1. HAMAP-Rule MF_00097
Subunit structure	Monomer.
Induction	Is weakly repressed by THZ and not at all by thiamine. Ref.3
Miscellaneous	Thiamine phosphate synthase appears to proceed with a dissociative mechanism (SN1 like) in which the pyrimidine pyrophosphate dissociates to give a reactive pyrimidine intermediate which is then trapped by the thiazole moiety. HAMAP-Rule MF_00097
Sequence similarities	Belongs to the thiamine-phosphate synthase family.
Biophysicochemical properties	Kinetic parameters: KM=0.7 µM for HMP-PP Ref.3 KM=1.2 µM for THZ-P Vmax=0.7 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Thiamine biosynthesis
Ligand	Magnesium Metal-binding
Molecular function	Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	thiamine biosynthetic process Inferred from electronic annotation. Source: HAMAP thiamine diphosphate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Molecular_function	magnesium ion binding Inferred from electronic annotation. Source: HAMAP thiamine-phosphate diphosphorylase activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 222

222

Thiamine-phosphate synthase HAMAP-Rule MF_00097

PRO_0000156995

Regions

Region

44 – 48

5

HMP-PP binding HAMAP-Rule MF_00097

Region

143 – 145

3

THZ-P binding HAMAP-Rule MF_00097

Region

195 – 196

2

THZ-P binding HAMAP-Rule MF_00097

Sites

Metal binding

80

1

Magnesium

Metal binding

99

1

Magnesium

Binding site

79

1

HMP-PP

Binding site

117

1

HMP-PP

Binding site

146

1

HMP-PP

Binding site

175

1

THZ-P; via amide nitrogen

Experimental info

Mutagenesis

117

1

S → A: 8000-fold reduction in catalytic activity. Ref.4

Secondary structure

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222

Helix Strand Turn

Details...

Helix

6 – 12

7

Beta strand

15 – 19

5

Helix

21 – 23

3

Helix

28 – 38

11

Beta strand

41 – 45

5

Helix

55 – 72

18

Beta strand

76 – 80

5

Helix

82 – 88

7

Beta strand

91 – 95

5

Beta strand

97 – 99

3

Helix

102 – 109

8

Beta strand

112 – 118

7

Helix

121 – 130

10

Beta strand

133 – 137

5

Beta strand

145 – 148

4

Helix

156 – 163

8

Beta strand

170 – 175

6

Turn

178 – 180

3

Helix

182 – 186

5

Beta strand

190 – 195

6

Helix

196 – 199

4

Beta strand

201 – 203

3

Helix

204 – 221

18

Sequences

	Sequence		Length	Mass (Da)
	P39594 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: BF09EB73866F4FB4	FASTA	222	23,681
	10 20 30 40 50 60 MTRISREMMK ELLSVYFIMG SNNTKADPVT VVQKALKGGA TLYQFREKGG DALTGEARIK 70 80 90 100 110 120 FAEKAQAACR EAGVPFIVND DVELALNLKA DGIHIGQEDA NAKEVRAAIG DMILGVSAHT 130 140 150 160 170 180 MSEVKQAEED GADYVGLGPI YPTETKKDTR AVQGVSLIEA VRRQGISIPI VGIGGITIDN 190 200 210 220 AAPVIQAGAD GVSMISAISQ AEDPESAARK FREEIQTYKT GR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bacillus subtilis genome project: cloning and sequencing of the 97 kb region from 325 degrees to 333 degrees." Glaser P., Kunst F., Arnaud M., Coudart M.P., Gonzales W., Hullo M.-F., Ionescu M., Lubochinsky B., Marcelino L., Moszer I., Presecan E., Santana M., Schneider E., Schweizer J., Vertes A., Rapoport G., Danchin A. Mol. Microbiol. 10:371-384(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 168.
[2]	"The complete genome sequence of the Gram-positive bacterium Bacillus subtilis." Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V., Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R., Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S., Bruschi C.V. , Caldwell B., Capuano V., Carter N.M., Choi S.-K., Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F., Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D., Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M., Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P., Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K., Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S., Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y., Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G., Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J., Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C., Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S., Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B., Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S., Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M., Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y., Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J., Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A., Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M., Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S., Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E., Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K., Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E., Yoshikawa H., Danchin A. Nature 390:249-256(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: 168.
[3]	"Characterization of the Bacillus subtilis thiC operon involved in thiamine biosynthesis." Zhang Y., Taylor S.V., Chiu H.-J., Begley T.P. J. Bacteriol. 179:3030-3035(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, KINETIC PARAMETERS, INDUCTION. Strain: 168 / CU1065.
[4]	"Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative mechanism." Reddick J.J., Nicewonger R., Begley T.P. Biochemistry 40:10095-10102(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY, MUTAGENESIS OF SER-117, REACTION MECHANISM. Strain: 168 / CU1065.
[5]	"Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolution." Chiu H.-J., Reddick J.J., Begley T.P., Ealick S.E. Biochemistry 38:6460-6470(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH THIAMINE PHOSPHATE AND MAGNESIUM PYROPHOSPHATE. Strain: 168 / CU1065.
[6]	"Structural characterization of the enzyme-substrate, enzyme-intermediate, and enzyme-product complexes of thiamin phosphate synthase." Peapus D.H., Chiu H.J., Campobasso N., Reddick J.J., Begley T.P., Ealick S.E. Biochemistry 40:10103-10114(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-117 IN COMPLEXES WITH SUBSTRATE; PRODUCTS AND INTERMEDIATES. Strain: 168 / CU1065.
[7]	"Crystal structure and kinetic characterization of Bacillus subtilis thiamin phosphate synthase with a carboxylated thiazole phosphate." McCulloch K.M., Hanes J.W., Abdelwahed S., Mahanta N., Hazra A., Ishida K., Begley T.P., Ealick S.E. Submitted (JUL-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X73124 Genomic DNA. Translation: CAA51582.1.
AL009126 Genomic DNA. Translation: CAB15855.1.

PIR

S39681.

RefSeq

NP_391708.1. NC_000964.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G4E	X-ray	1.60	A/B	1-222	[»]
1G4P	X-ray	2.50	A/B	1-222	[»]
1G4S	X-ray	1.70	A/B	1-222	[»]
1G4T	X-ray	1.55	A/B	1-222	[»]
1G67	X-ray	1.40	A/B	1-222	[»]
1G69	X-ray	1.50	A/B	1-222	[»]
1G6C	X-ray	1.40	A/B	1-222	[»]
2TPS	X-ray	1.25	A/B	1-222	[»]
3O15	X-ray	1.95	A	1-222	[»]
3O16	X-ray	2.10	A	1-222	[»]

ProteinModelPortal

P39594.

SMR

P39594. Positions 1-222.

ModBase

Search...

Protein-protein interaction databases

STRING

224308.BSU38290.

Proteomic databases

PaxDb

P39594.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

CAB15855; CAB15855; BSU38290.

GeneID

937316.

KEGG

bsu:BSU38290.

PATRIC

18979704. VBIBacSub10457_4014.

Organism-specific databases

GenoList

BSU38290. [Micado]

Phylogenomic databases

eggNOG

COG0352.

HOGENOM

HOG000155781.

KO

K00788.

OMA

SINELEF.

ProtClustDB

PRK00043.

Enzyme and pathway databases

BioCyc

BSUB:BSU38290-MONOMER.
MetaCyc:BSU38290-MONOMER.

UniPathway

UPA00060; UER00141.

Family and domain databases

Gene3D

3.20.20.70. 1 hit.

HAMAP

MF_00097. TMP_synthase.

InterPro

IPR013785. Aldolase_TIM.
IPR022998. ThiaminP_synth_SF.
IPR003733. TMP_synthase.
[Graphical view]

Pfam

PF02581. TMP-TENI. 1 hit.
[Graphical view]

SUPFAM

SSF51391. TMP_synthase. 1 hit.

TIGRFAMs

TIGR00693. thiE. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P39594.

Entry information

Entry name

THIE_BACSU

Accession

Primary (citable) accession number: P39594

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program