EzCatDB: S00453
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DB codeS00453
RLCP classification3.103.78010.320 : Transfer
CATH domainDomain 13.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineCatalytic domain
E.C.2.7.1.50

CATH domainRelated DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineS00534,S00541,S00678,S00705,S00903,S00904,S00905,D00416

Enzyme Name
UniProtKBKEGG

P39593
Protein nameHydroxyethylthiazole kinasehydroxyethylthiazole kinase
hydroxyethylthiazole kinase (phosphorylating)
4-methyl-5-(beta-hydroxyethyl)thiazole kinase
SynonymsEC 2.7.1.50
4-methyl-5-beta-hydroxyethylthiazole kinase
Thz kinase
TH kinase
RefSeqNP_391709.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PfamPF02110 (HK)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00730Thiamine metabolism

UniProtKB:Accession NumberP39593
Entry nameTHIM_BACSU
ActivityATP + 4-methyl-5-(2-hydroxyethyl)thiazole = ADP + 4-methyl-5-(2-phosphonooxyethyl)thiazole.
SubunitHomotrimer.
Subcellular location
CofactorBinds 2 magnesium ions per subunit. The second one is coordinated to ATP but its significance is unclear.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C04294C00008C04327
CompoundMagnesiumATP4-Methyl-5-(2-hydroxyethyl)-thiazoleADP4-Methyl-5-(2-phosphoethyl)-thiazole
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (with nitrogen atoms),carbohydrateamine group,nucleotidearomatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI18420
15422
17957
16761
17857
PubChem888
5957
1136
6022
1137
             
1c3qAUnboundUnboundBound:TZEUnboundUnbound
1c3qBUnboundUnboundBound:TZEUnboundUnbound
1c3qCUnboundUnboundBound:TZEUnboundUnbound
1ekkAUnboundUnboundBound:TZEUnboundUnbound
1ekkBUnboundUnboundBound:TZEUnboundUnbound
1ekqAUnboundUnboundUnboundUnboundUnbound
1ekqBUnboundUnboundUnboundUnboundUnbound
1esjAUnboundUnboundUnboundUnboundUnbound
1esjBUnboundUnboundUnboundUnboundUnbound
1esjCUnboundUnboundUnboundUnboundUnbound
1esqABound:_MGBound:ATPUnboundUnboundBound:TZP
1esqBBound:_MGBound:ATPUnboundUnboundBound:TZP
1esqCBound:_MGBound:ATPUnboundUnboundBound:TZP

Active-site residues
resource
Swiss-prot;P39593
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
1c3qACYS 198
ASP 94;GLU 126(Magnesium binding)
 
 
1c3qBCYS 198
ASP 94;GLU 126(Magnesium binding)
 
 
1c3qCCYS 198
ASP 94;GLU 126(Magnesium binding)
 
 
1ekkACSW 198
ASP 94;GLU 126(Magnesium binding)
CSW 198(Double oxidized)
 
1ekkBCSW 198
ASP 94;GLU 126(Magnesium binding)
CSW 198(Double oxidized)
 
1ekqACSW 198
ASP 94;GLU 126(Magnesium binding)
CSW 198(Double oxidized)
 
1ekqBCSW 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
ReferencesSectionsNo. of steps in catalysis
[5]p.7876, Fig.9

references
[1]
PubMed ID8394314
JournalJ Bacteriol
Year1993
Volume175
Pages5153-8
AuthorsKawasaki Y
TitleCopurification of hydroxyethylthiazole kinase and thiamine-phosphate pyrophosphorylase of Saccharomyces cerevisiae: characterization of hydroxyethylthiazole kinase as a bifunctional enzyme in the thiamine biosynthetic pathway.
[2]
PubMed ID7982968
JournalJ Biol Chem
Year1994
Volume269
Pages30510-6
AuthorsNosaka K, Nishimura H, Kawasaki Y, Tsujihara T, Iwashima A
TitleIsolation and characterization of the THI6 gene encoding a bifunctional thiamin-phosphate pyrophosphorylase/hydroxyethylthiazole kinase from Saccharomyces cerevisiae.
[3]
CommentsCHARACTERIZATION
PubMed ID9139923
JournalJ Bacteriol
Year1997
Volume179
Pages3030-5
AuthorsZhang Y, Taylor SV, Chiu HJ, Begley TP
TitleCharacterization of the Bacillus subtilis thiC operon involved in thiamine biosynthesis.
Related UniProtKBP39593
[4]
PubMed ID10075431
JournalMicrobiology
Year1999
Volume145
Pages495-501
AuthorsMizote T, Tsuda M, Smith DD, Nakayama H, Nakazawa T
TitleCloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS)
PubMed ID10891066
JournalBiochemistry
Year2000
Volume39
Pages7868-77
AuthorsCampobasso N, Mathews II, Begley TP, Ealick SE
TitleCrystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus subtilis at 1.5 A resolution.
Related PDB1c3q,1esq,1esj,1ekq,1ekk
Related UniProtKBP39593

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.

createdupdated
2003-07-142009-03-19


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