EzCatDB: S00705
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DB codeS00705
RLCP classification3.103.80570.321 : Transfer
3.133.91040.388 : Transfer
CATH domainDomain 13.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineCatalytic domain
E.C.2.7.1.49,2.7.4.7
CSA1jxh

CATH domainRelated DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanineS00534,S00541,S00678,S00903,S00904,S00905,S00453,D00416

Enzyme Name
UniProtKBKEGG

P55882Q7SIA0
Protein namePhosphomethylpyrimidine kinase
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)

SynonymsEC 2.7.4.7
HMP-phosphate kinase
HMP-P kinase
HMPP kinase
Transferase
RefSeqNP_461090.1 (Protein)
NC_003197.1 (DNA/RNA sequence)

PfamPF08543 (Phos_pyr_kin)
[Graphical view]
PF08543 (Phos_pyr_kin)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00730Thiamine metabolism2.7.1.49,2.7.4.7

UniProtKB:Accession NumberP55882Q7SIA0
Entry nameTHID_SALTYQ7SIA0_THETH
ActivityATP + 4-amino-2-methyl-5-phosphomethylpyrimidine = ADP + 4-amino-2-methyl-5-diphosphomethylpyrimidine.
SubunitHomodimer.
Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C01279C04556C00008C04556C04752
E.C.2.7.1.49,2.7.4.72.7.1.49,2.7.4.72.7.1.492.7.4.72.7.1.49,2.7.4.72.7.1.492.7.4.7
CompoundMagnesiumATP4-amino-5-hydroxymethyl-2-methylpyrimidine(4-amino-2-methylpyrimidin-5-yl)methyl phosphateADP(4-amino-2-methylpyrimidin-5-yl)methyl phosphate(4-amino-2-methylpyrimidin-5-yl)methyl diphosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamine group,aromatic ring (with nitrogen atoms),carbohydrateamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ionamine group,nucleotideamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ionamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI18420
15422
16892
18032
16761
18032
16629
PubChem888
5957
777
216
6022
216
217
               
1jxhA00UnboundAnalogue:SO4-SO4UnboundUnboundUnboundUnboundUnbound
1jxhB00UnboundAnalogue:SO4-SO4UnboundUnboundUnboundUnboundUnbound
1jxiA00UnboundAnalogue:SO4-SO4Bound:HMHUnboundUnboundUnboundUnbound
1jxiB00UnboundAnalogue:SO4-SO4Bound:HMHUnboundUnboundUnboundUnbound
1ub0A00UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [1], [2], [3], [6]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
           
1jxhA00LYS 176
THR 208(Magnesium binding)
GLY 210;THR 211;GLY 212;CYS 213
1jxhB00LYS 176
THR 208(Magnesium binding)
GLY 210;THR 211;GLY 212;CYS 213
1jxiA00LYS 176
THR 208(Magnesium binding)
GLY 210;THR 211;GLY 212;CYS 213
1jxiB00LYS 176
THR 208(Magnesium binding)
GLY 210;THR 211;GLY 212;CYS 213
1ub0A00LYS 173
THR 205(Magnesium binding)
GLY 207;THR 208;GLY 209;CYS 210

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.7876-7877
[3]Fig.7, p.229-232

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
PubMed ID9519409
JournalStructure
Year1998
Volume6
Pages183-93
AuthorsSigrell JA, Cameron AD, Jones TA, Mowbray SL
TitleStructure 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 PDB1rkd
Related UniProtKBP0A9J6
[2]
CommentsX-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, HOMOTRIMERIZATION, AND MUTAGENESIS OF CYS-198.
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
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-266.
PubMed ID11839308
JournalStructure
Year2002
Volume10
Pages225-35
AuthorsCheng G, Bennett EM, Begley TP, Ealick SE
TitleCrystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution.
Related PDB1jxh,1jxi
Related UniProtKBP55882
[4]
PubMed ID14675553
JournalCurr Opin Struct Biol
Year2003
Volume13
Pages739-47
AuthorsSettembre E, Begley TP, Ealick SE
TitleStructural biology of enzymes of the thiamin biosynthesis pathway.
[5]
JournalInt J Mol Sci
Year2004
Volume5
Pages141-153
AuthorsEdyta Dyguda, Borys Szefczyk and W. A. Sokalski
TitleThe Mechanism of Phosphoryl Transfer Reaction and the Role of Active Site Residues on the Basis of Ribokinase-Like Kinases
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
PubMed ID15458630
JournalStructure
Year2004
Volume12
Pages1809-21
AuthorsZhang Y, Dougherty M, Downs DM, Ealick SE
TitleCrystal structure of an aminoimidazole riboside kinase from Salmonella enterica: implications for the evolution of the ribokinase superfamily.
Related PDB1tyy,1tz3,1tz6
Related UniProtKBQ8ZKR2
[7]
PubMed ID16978644
JournalJ Mol Biol
Year2006
Volume363
Pages520-30
AuthorsNewman JA, Das SK, Sedelnikova SE, Rice DW
TitleThe crystal structure of an ADP complex of Bacillus subtilis pyridoxal kinase provides evidence for the parallel emergence of enzyme activity during evolution.
Related PDB2i5b

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.

createdupdated
2009-08-282011-11-17


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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