EzCatDB: S00680
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DB codeS00680
RLCP classification3.103.70035.360 : Transfer
CATH domainDomain 13.40.50.300 : Rossmann foldCatalytic domain
E.C.2.7.1.48

CATH domainRelated DB codes (homologues)
3.40.50.300 : Rossmann foldS00527,S00547,S00548,S00550,S00554,S00555,S00671,S00672,S00676,S00682,S00913,S00914,S00301,S00302,S00303,S00304,S00307,S00308,S00305,S00306,S00309,S00310,S00311,M00114,M00199,D00129,D00130,D00540,M00186

Enzyme Name
UniProtKBKEGG

Q9BZX2Q9HA47
Protein nameUridine-cytidine kinase 2Uridine-cytidine kinase 1Uridine kinase
Pyrimidine ribonucleoside kinase
Uridine-cytidine kinase
Uridine kinase (phosphorylating)
Uridine phosphokinase
SynonymsUCK 2
EC 2.7.1.48
Uridine monophosphokinase 2
Cytidine monophosphokinase 2
UCK 1
EC 2.7.1.48
Uridine monophosphokinase 1
Cytidine monophosphokinase 1
RefSeqNP_036606.2 (Protein)
NM_012474.4 (DNA/RNA sequence)
NP_001129426.1 (Protein)
NM_001135954.1 (DNA/RNA sequence)
NP_001248379.1 (Protein)
NM_001261450.1 (DNA/RNA sequence)
NP_001248380.1 (Protein)
NM_001261451.1 (DNA/RNA sequence)
NP_113620.1 (Protein)
NM_031432.2 (DNA/RNA sequence)
PfamPF00485 (PRK)
[Graphical view]
PF00485 (PRK)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism
MAP00983Drug metabolism - other enzymes

UniProtKB:Accession NumberQ9BZX2Q9HA47
Entry nameUCK2_HUMANUCK1_HUMAN
ActivityATP + uridine = ADP + UMP.,ATP + cytidine = ADP + CMP.ATP + uridine = ADP + UMP.,ATP + cytidine = ADP + CMP.
SubunitHomotetramer.
Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00299C00475C00008C00105C00055
CompoundMagnesiumATPUridineCytidineADPUMPCMP
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamide group,nucleosideamine group,nucleosideamine group,nucleotideamide group,nucleotideamine group,nucleotide
ChEBI18420
15422
16704
17562
16761
16695
17361
PubChem888
5957
6029
6175
6022
6030
6131
               
1udwA00UnboundUnboundUnboundUnboundUnboundUnboundAnalogue:CTP
1udwB00UnboundUnboundUnboundUnboundUnboundUnboundAnalogue:CTP
1ueiA00UnboundUnboundUnboundUnboundUnboundAnalogue:UTPUnbound
1ueiB00UnboundUnboundUnboundUnboundUnboundAnalogue:UTPUnbound
1uejA00UnboundUnboundUnboundBound:CTNUnboundUnboundUnbound
1uejB00UnboundUnboundUnboundBound:CTNUnboundUnboundUnbound
1ufqA00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ufqB00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ufqC00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ufqD00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1uj2A00Bound:_MGUnboundUnboundUnboundBound:ADPUnboundBound:C5P
1uj2B00Bound:_MGUnboundUnboundUnboundBound:ADPUnboundBound:C5P
1xrjA00Bound:_MGUnboundUnboundUnboundBound:ADPUnboundBound:C5P
1xrjB00Bound:_MGUnboundUnboundUnboundBound:ADPUnboundBound:C5P
2jeoA00UnboundUnboundUnboundUnboundUnboundUnboundUnbound
2uvqA00UnboundUnboundUnboundUnboundBound:ADPUnboundUnbound

Active-site residues
resource
literature [3] & [5]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1udwA00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 45-52
1udwB00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 47-50
1ueiA00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 45-52
1ueiB00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 47-50
1uejA00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 47-52
1uejB00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
invisible 47-52
1ufqA00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1ufqB00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1ufqC00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1ufqD00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1uj2A00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1uj2B00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1xrjA00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
1xrjB00LYS 33;ASP 62;ARG 169;ARG 174
SER 34(Magnesium binding)
ALA 30;SER 31;GLY 32;LYS 33
 
2jeoA00LYS 36;ASP 65;ARG 172;       
SER 37(Magnesium binding)
ALA 33;SER 34;GLY 35;LYS 36
invisible 176-178
2uvqA00LYS 36;ASP 65;ARG 172;       
SER 37(Magnesium binding)
ALA 33;SER 34;GLY 35;LYS 36
invisible 176-178

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.762
[5]Fig.1, p. 2716, Fig.7, p.2720

references
[1]
PubMed ID7914091
JournalBiochemistry
Year1994
Volume33
Pages9343-50
AuthorsCharlier HA Jr, Runquist JA, Miziorko HM
TitleEvidence supporting catalytic roles for aspartate residues in phosphoribulokinase.
[2]
PubMed ID11306702
JournalMol Pharmacol
Year2001
Volume59
Pages1181-6
AuthorsVan Rompay AR, Norda A, Linden K, Johansson M, Karlsson A
TitlePhosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases.
[3]
PubMed ID15130468
JournalStructure
Year2004
Volume12
Pages751-64
AuthorsSuzuki NN, Koizumi K, Fukushima M, Matsuda A, Inagaki F
TitleStructural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
Related PDB1udw,1uei,1uej,1ufq,iuj2
Related UniProtKBQ9BZX2
[4]
PubMed ID15735337
JournalActa Crystallogr D Biol Crystallogr
Year2005
Volume61
Pages278-84
AuthorsAppleby TC, Larson G, Cheney IW, Walker H, Wu JZ, Zhong W, Hong Z, Yao N
TitleStructure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating-anode X-ray generator and a single samarium derivative.
Related PDB1xrj
Related UniProtKBQ9BZX2
[5]
PubMed ID19532987
JournalOrg Biomol Chem
Year2009
Volume7
Pages2716-24
AuthorsSmith AJ, Li Y, Houk KN
TitleQuantum mechanics/molecular mechanics investigation of the mechanism of phosphate transfer in human uridine-cytidine kinase 2.

comments
This enzyme is homologous to shikimate kinase (S00304 in EzCatDB) and adenylate kinase (S00305 in EzCatDB).
According to the literature [3], the reaction proceeds as follows:
(0) Magnesium ion, which is bound to Ser34, is bridging beta- and gamma-phosphate groups of ATP. Arg169 and Arg174 interact with the transferred gamma-phosphate, whereas Lys33 interacts with both beta- and gamma-phosphate groups. Meanwhile, mainchain amide groups of Ala30-Ser31-Gly32-Lys33 interact mainly with beta-phosphate group of ATP.
(1) Asp62 acts as a general base to deprotonate the acceptor group, 5'-hydroxyl group of uridine or cytidine.
(2) The activated 5'-hydroxyl oxygen makes a nucleophilic attack on the gamma-phosphate group, leading to transition-state. The transferred gamma-phsophate group in the transition state can be stabilized by Lys33, Arg169 and Arg174, along with the magnesium ion, whereas the leaving alpha- and beta-phosphate groups can be stabilized by the mainchain amide groups and the magnesium ion.
(3) The reaction completes via SN2-like mechanism.

createdupdated
2009-08-112011-12-15


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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