DB code: S00453

RLCP classification 3.103.78010.320 : Transfer
CATH domain 3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine Catalytic domain
E.C. 2.7.1.50
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine S00534 S00541 S00678 S00705 S00903 S00904 S00905 D00416

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P39593 Hydroxyethylthiazole kinase
EC 2.7.1.50
4-methyl-5-beta-hydroxyethylthiazole kinase
Thz kinase
TH kinase
NP_391709.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF02110 (HK)
[Graphical View]

KEGG enzyme name
hydroxyethylthiazole kinase
hydroxyethylthiazole kinase (phosphorylating)
4-methyl-5-(beta-hydroxyethyl)thiazole kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P39593 THIM_BACSU ATP + 4-methyl-5-(2-hydroxyethyl)thiazole = ADP + 4-methyl-5-(2-phosphonooxyethyl)thiazole. Homotrimer. Binds 2 magnesium ions per subunit. The second one is coordinated to ATP but its significance is unclear.

KEGG Pathways
Map code Pathways E.C.
MAP00730 Thiamine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C04294 C00008 C04327
E.C.
Compound Magnesium ATP 4-Methyl-5-(2-hydroxyethyl)-thiazole ADP 4-Methyl-5-(2-phosphoethyl)-thiazole
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide aromatic ring (with nitrogen atoms),carbohydrate amine group,nucleotide aromatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		17957
 17957
 		16761
 16761
 		17857
 17857
PubChem 888
 888
 		5957
 5957
 		1136
 1136
 		6022
 6022
 		1137
 1137
1c3qA Unbound Unbound Bound:TZE Unbound Unbound
1c3qB Unbound Unbound Bound:TZE Unbound Unbound
1c3qC Unbound Unbound Bound:TZE Unbound Unbound
1ekkA Unbound Unbound Bound:TZE Unbound Unbound
1ekkB Unbound Unbound Bound:TZE Unbound Unbound
1ekqA Unbound Unbound Unbound Unbound Unbound
1ekqB Unbound Unbound Unbound Unbound Unbound
1esjA Unbound Unbound Unbound Unbound Unbound
1esjB Unbound Unbound Unbound Unbound Unbound
1esjC Unbound Unbound Unbound Unbound Unbound
1esqA Bound:_MG Bound:ATP Unbound Unbound Bound:TZP
1esqB Bound:_MG Bound:ATP Unbound Unbound Bound:TZP
1esqC Bound:_MG Bound:ATP Unbound Unbound Bound:TZP

Reference for Active-site residues
resource references E.C.
Swiss-prot;P39593

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1c3qA CYS 198 ASP 94;GLU 126(Magnesium binding)
1c3qB CYS 198 ASP 94;GLU 126(Magnesium binding)
1c3qC CYS 198 ASP 94;GLU 126(Magnesium binding)
1ekkA CSW 198 ASP 94;GLU 126(Magnesium binding) CSW 198(Double oxidized)
1ekkB CSW 198 ASP 94;GLU 126(Magnesium binding) CSW 198(Double oxidized)
1ekqA CSW 198 ASP 94;GLU 126(Magnesium binding) CSW 198(Double oxidized)
1ekqB CSW 198 ASP 94;GLU 126(Magnesium binding) CSW 198(Double oxidized)
1esjA ASP 94;GLU 126(Magnesium binding) mutant C198S
1esjB ASP 94;GLU 126(Magnesium binding) mutant C198S
1esjC ASP 94;GLU 126(Magnesium binding) mutant C198S
1esqA ASP 94;GLU 126(Magnesium binding) mutant C198S
1esqB ASP 94;GLU 126(Magnesium binding) mutant C198S
1esqC ASP 94;GLU 126(Magnesium binding) mutant C198S

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
p.7876, Fig.9

References
[1]
Resource
Comments
Medline ID
PubMed ID 8394314
Journal J Bacteriol
Year 1993
Volume 175
Pages 5153-8
Authors Kawasaki Y
Title Copurification of hydroxyethylthiazole kinase and thiamine-phosphate pyrophosphorylase of Saccharomyces cerevisiae: characterization of hydroxyethylthiazole kinase as a bifunctional enzyme in the thiamine biosynthetic pathway.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7982968
Journal J Biol Chem
Year 1994
Volume 269
Pages 30510-6
Authors Nosaka K, Nishimura H, Kawasaki Y, Tsujihara T, Iwashima A
Title Isolation and characterization of the THI6 gene encoding a bifunctional thiamin-phosphate pyrophosphorylase/hydroxyethylthiazole kinase from Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[3]
Resource
Comments CHARACTERIZATION
Medline ID
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 PDB
Related UniProtKB P39593
[4]
Resource
Comments
Medline ID
PubMed ID 10075431
Journal Microbiology
Year 1999
Volume 145
Pages 495-501
Authors Mizote T, Tsuda M, Smith DD, Nakayama H, Nakazawa T
Title Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS)
Medline ID
PubMed ID 10891066
Journal Biochemistry
Year 2000
Volume 39
Pages 7868-77
Authors Campobasso N, Mathews II, Begley TP, Ealick SE
Title Crystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus subtilis at 1.5 A resolution.
Related PDB 1c3q 1esq 1esj 1ekq 1ekk
Related UniProtKB P39593

Comments
According to the literature [5], Cys198 was initially considered to be a general base, which activates the acceptor, thiazole alcohol. In the reaction, the nucleophilicity of the acceptor alcohol might be increased by a proton relay system (Cys198-water-magnesium), whilst the electrophilicity of the transferred group, the gamma-phosphate, can be enhanced by coordination of one of the gamma-phosphate oxygen atoms to the magnesium ion and by hydrogen bonding between a second phosphate oxygen and the amide protons of Gly197 and Cys198.
However, mutagenesis analyses (C198S and C198A mutant, showing 20% and 40% activitiy of wild type, respectively) suggested that an alternative base must exist (see [5]). Thus, the paper [5] suggested that one of the gamma-phosphate oxygen atoms may act as the general base that will activate the alcohol.

Created Updated
2003-07-14 2009-03-19