DB code: S00705

RLCP classification 3.103.80570.321 : Transfer
3.133.91040.388 : Transfer
CATH domain 3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine Catalytic domain
E.C. 2.7.1.49 2.7.4.7
CSA 1jxh
M-CSA 1jxh
MACiE

CATH domain Related DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine S00534 S00541 S00678 S00903 S00904 S00905 S00453 D00416

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P55882 Phosphomethylpyrimidine kinase
EC 2.7.4.7
HMP-phosphate kinase
HMP-P kinase
HMPP kinase
NP_461090.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF08543 (Phos_pyr_kin)
[Graphical View]
Q7SIA0
Transferase
PF08543 (Phos_pyr_kin)
[Graphical View]

KEGG enzyme name
Hydroxymethylpyrimidine kinase
(EC 2.7.1.49 )
Hydroxymethylpyrimidine kinase (phosphorylating)
(EC 2.7.1.49 )
Phosphomethylpyrimidine kinase
(EC 2.7.4.7 )
Hydroxymethylpyrimidine phosphokinase
(EC 2.7.4.7 )
ATP:4-amino-2-methyl-5-phosphomethylpyrimidine phosphotransferase
(EC 2.7.4.7 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P55882 THID_SALTY ATP + 4-amino-2-methyl-5-phosphomethylpyrimidine = ADP + 4-amino-2-methyl-5-diphosphomethylpyrimidine. Homodimer.
Q7SIA0 Q7SIA0_THETH

KEGG Pathways
Map code Pathways E.C.
MAP00730 Thiamine metabolism 2.7.1.49 2.7.4.7

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C01279 C04556 C00008 C04556 C04752
E.C. 2.7.1.49
2.7.4.7
2.7.1.49
2.7.4.7
2.7.1.49
2.7.4.7
2.7.1.49
2.7.4.7
2.7.1.49
2.7.4.7
Compound Magnesium ATP 4-amino-5-hydroxymethyl-2-methylpyrimidine (4-amino-2-methylpyrimidin-5-yl)methyl phosphate ADP (4-amino-2-methylpyrimidin-5-yl)methyl phosphate (4-amino-2-methylpyrimidin-5-yl)methyl diphosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amine group,aromatic ring (with nitrogen atoms),carbohydrate amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amine group,nucleotide amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16892
 16892
 		18032
 18032
 		16761
 16761
 		18032
 18032
 		16629
 16629
PubChem 888
 888
 		5957
 5957
 		777
 777
 		216
 216
 		6022
 6022
 		216
 216
 		217
 217
1jxhA00 Unbound Analogue:SO4-SO4 Unbound Unbound Unbound Unbound Unbound
1jxhB00 Unbound Analogue:SO4-SO4 Unbound Unbound Unbound Unbound Unbound
1jxiA00 Unbound Analogue:SO4-SO4 Bound:HMH Unbound Unbound Unbound Unbound
1jxiB00 Unbound Analogue:SO4-SO4 Bound:HMH Unbound Unbound Unbound Unbound
1ub0A00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1], [2], [3], [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1jxhA00 LYS 176 THR 208(Magnesium binding) GLY 210;THR 211;GLY 212;CYS 213
1jxhB00 LYS 176 THR 208(Magnesium binding) GLY 210;THR 211;GLY 212;CYS 213
1jxiA00 LYS 176 THR 208(Magnesium binding) GLY 210;THR 211;GLY 212;CYS 213
1jxiB00 LYS 176 THR 208(Magnesium binding) GLY 210;THR 211;GLY 212;CYS 213
1ub0A00 LYS 173 THR 205(Magnesium binding) GLY 207;THR 208;GLY 209;CYS 210

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.7876-7877
[3]
Fig.7, p.229-232

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
Medline ID
PubMed ID 9519409
Journal Structure
Year 1998
Volume 6
Pages 183-93
Authors Sigrell JA, Cameron AD, Jones TA, Mowbray SL
Title Structure of Escherichia coli ribokinase in complex with ribose and dinucleotide determined to 1.8 A resolution: insights into a new family of kinase structures.
Related PDB 1rkd
Related UniProtKB P0A9J6
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, HOMOTRIMERIZATION, AND MUTAGENESIS OF CYS-198.
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
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-266.
Medline ID
PubMed ID 11839308
Journal Structure
Year 2002
Volume 10
Pages 225-35
Authors Cheng G, Bennett EM, Begley TP, Ealick SE
Title Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution.
Related PDB 1jxh 1jxi
Related UniProtKB P55882
[4]
Resource
Comments
Medline ID
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.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID
Journal Int J Mol Sci
Year 2004
Volume 5
Pages 141-153
Authors Edyta Dyguda, Borys Szefczyk and W. A. Sokalski
Title The Mechanism of Phosphoryl Transfer Reaction and the Role of Active Site Residues on the Basis of Ribokinase-Like Kinases
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID
PubMed ID 15458630
Journal Structure
Year 2004
Volume 12
Pages 1809-21
Authors Zhang Y, Dougherty M, Downs DM, Ealick SE
Title Crystal structure of an aminoimidazole riboside kinase from Salmonella enterica: implications for the evolution of the ribokinase superfamily.
Related PDB 1tyy 1tz3 1tz6
Related UniProtKB Q8ZKR2
[7]
Resource
Comments
Medline ID
PubMed ID 16978644
Journal J Mol Biol
Year 2006
Volume 363
Pages 520-30
Authors Newman JA, Das SK, Sedelnikova SE, Rice DW
Title The crystal structure of an ADP complex of Bacillus subtilis pyridoxal kinase provides evidence for the parallel emergence of enzyme activity during evolution.
Related PDB 2i5b
Related UniProtKB

Comments
This enzyme belongs to the ribokinase superfamily (EC 2.7.1.15, S00534 & S00541 in EzCatDB)(see [3]).
This enzyme catalyzes the following consecutive reactions (see [3]):
(A) Transfer of gamma-phosphate of ATP to hydroxyl group of HMP:
(A0) Magnesium ion, which is bound to Thr208, coordinates with both the beta- and gamma-phosphate groups of ATP, thereby stabilizing ADP as a leaving group and enhancing the reactivity of gamma-phosphate group. Moreover, anion hole composed of mainchain amide groups of Gly210-Thr211-Gly212-Cys213 stabilizes the beta- and gamma-phosphate groups. Thereby, the transition state can be stabilized.
(A1) An oxygen atom of gamma-phosphate group of ATP acts as a general base to deprotonate the hydroxyl group of HMP.
(A2) The activated hydroxyl oxygen of HMP makes a nucleophilic attack on the gamma-phosphate of ATP, to produce HMP-P. This reaction proceeds via SN2 mechanism.
(B) Transfer of gamma-phosphate of ATP to phosphate group of HMP-P:
(B0) The phosphate of HMP is repositioned, and the gamma-phosphate group swing toward hte HMP-P substrate. Magnesium ion, bound to Thr208 stabilizes the negative charge on ADP as a leaving group, and the transferred gamma-phosphate group. Moreover, anion hole stabilizes the beta- and gamma-phosphate groups, along with the sidechain of Lys176. Thereby, the transition state can be stabilized.
(B1) The phosphate of HMP makes a nucleophilic attack on the gamma-phosphate of ATP, to produce HMP-P. This reaction proceeds via SN2 mechanism.

Created Updated
2009-08-28 2011-11-17