EzCatDB: S00308
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DB codeS00308
RLCP classification3.133.90030.392 : Transfer
CATH domainDomain 13.40.50.300 : Rossmann foldCatalytic domain
E.C.2.7.4.14

CATH domainRelated DB codes (homologues)
3.40.50.300 : Rossmann foldS00527,S00547,S00548,S00550,S00554,S00555,S00671,S00672,S00676,S00680,S00682,S00913,S00914,S00301,S00302,S00303,S00304,S00307,S00305,S00306,S00309,S00310,S00311,M00114,M00199,D00129,D00130,D00540,M00186

Enzyme Name
UniProtKBKEGG

P20425P30085
Protein nameCytidylate kinaseUMP-CMP kinasecytidylate kinase
deoxycytidylate kinase
deoxycytidylate kinase
CMP kinase
CTP:CMP phosphotransferase
dCMP kinase
deoxycytidine monophosphokinase
UMP-CMP kinase
ATP:UMP-CMP phosphotransferase
pyrimidine nucleoside monophosphate kinase
SynonymsEC 2.7.4.14
Deoxycytidylate kinase
UMP-CMP kinase
EC 2.7.4.14
Cytidylate kinase
Deoxycytidylate kinase
Cytidine monophosphate kinase
Uridine monophosphate kinase
Uridine monophosphate/cytidine monophosphate kinase
UMP/CMP kinase
UMP/CMPK
RefSeqXP_637196.1 (Protein)
XM_632104.1 (DNA/RNA sequence)
NP_001129612.1 (Protein)
NM_001136140.1 (DNA/RNA sequence)
NP_057392.1 (Protein)
NM_016308.2 (DNA/RNA sequence)
PfamPF00406 (ADK)
[Graphical view]
PF00406 (ADK)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism

UniProtKB:Accession NumberP20425P30085
Entry nameKCY_DICDIKCY_HUMAN
ActivityATP + (d)CMP = ADP + (d)CDP.ATP + (d)CMP = ADP + (d)CDP.
SubunitMonomer.
Subcellular location
Nucleus. Cytoplasm. Note=Mainly nuclear.
Cofactor
Magnesium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00305C00002C00055C00239C00008C00112C00705
CompoundMagnesiumATPCMPdCMPADPCDPdCDP
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamine group,nucleotideamine group,nucleotideamine group,nucleotideamine group,nucleotideamine group,nucleotide
ChEBI18420
15422
17361
15918
16761
17239
28846

PubChem888
5957
6131
13945
6022
6132
150855

                
1qf9ABound:_MGUnboundBound:C5PUnboundBound:ADPUnboundUnboundTransition-state-analogue:ALF
1ukdAUnboundAnalogue:UP5(ATP)Analogue:UP5(CMP)UnboundUnboundUnboundUnboundUnbound
1ukeABound:_MGAnalogue:UP5(ATP)Analogue:UP5(CMP)UnboundUnboundUnboundUnboundUnbound
2ukdABound:_MGUnboundBound:C5PUnboundBound:ADPUnboundUnboundUnbound
3ukdABound:_MGUnboundBound:C5PUnboundBound:ADPUnboundUnboundTransition-state-analogue:AF3
4ukdABound:_MGUnboundUnboundUnboundBound:ADPAnalogue:UDPUnboundTransition-state-analogue:BF2
5ukdABound:_MGUnboundBound:C5PUnboundBound:ADPUnboundUnboundTransition-state-analogue:AF3
1tevAUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
similar to S00305
pdbCatalytic residues
         
1qf9ALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
1ukdALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
1ukeALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
2ukdALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
3ukdALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
4ukdALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
5ukdALYS 19;ARG 42;ARG  93;ARG 131;ARG 137;ARG 148
1tevALYS 16;ARG 39;ARG  96;ARG 134;ARG 140;ARG 151

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.9724-9726
[6]Fig.1, p.9294-92952
[9]p.111-119
[10]Fig.1, Fig.22
[12]p.1106-1108

references
[1]
PubMed ID7729545
JournalFEBS Lett
Year1995
Volume363
Pages22-4
AuthorsWiesmuller L, Scheffzek K, Kliche W, Goody RS, Wittinghofer A, Reinstein J
TitleCrystallization and preliminary X-ray analysis of UMP/CMP-kinase from Dictyostelium discoideum with the specific bisubstrate inhibitor P1-(adenosine 5')-P5-(uridine 5')-pentaphosphate (UP5A).
[2]
PubMed ID7663945
JournalStructure
Year1995
Volume3
Pages483-90
AuthorsVonrhein C, Schlauderer GJ, Schulz GE
TitleMovie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
[3]
PubMed ID8576266
JournalJ Biol Chem
Year1996
Volume271
Pages2856-62
AuthorsBucurenci N, Sakamoto H, Briozzo P, Palibroda N, Serina L, Sarfati RS, Labesse G, Briand G, Danchin A, Barzu O, Gilles AM
TitleCMP kinase from Escherichia coli is structurally related to other nucleoside monophosphate kinases.
[4]
PubMed ID8703943
JournalBiochemistry
Year1996
Volume35
Pages9716-27
AuthorsScheffzek K, Kliche W, Wiesmuller L, Reinstein J
TitleCrystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) and Mg2+ at 2.2 A: implications for water-mediated specificity.
Related PDB1ukd,1uke
Related UniProtKBP20425
[5]
PubMed ID9126287
JournalArch Biochem Biophys
Year1997
Volume340
Pages144-53
AuthorsSchultz CP, Ylisastigui-Pons L, Serina L, Sakamoto H, Mantsch HH, Neuhard J, Barzu O, Gilles AM
TitleStructural and catalytic properties of CMP kinase from Bacillus subtilis: a comparative analysis with the homologous enzyme from Escherichia coli.
Related UniProtKBP0A6I0
[6]
PubMed ID9280438
JournalBiochemistry
Year1997
Volume36
Pages9290-6
AuthorsSchlichting I, Reinstein J
TitleStructures of active conformations of UMP kinase from Dictyostelium discoideum suggest phosphoryl transfer is associative.
Related PDB2ukd,3ukd,4ukd
Related UniProtKBP20425
[7]
PubMed ID9862805
JournalStructure
Year1998
Volume6
Pages1517-27
AuthorsBriozzo P, Golinelli-Pimpaneau B, Gilles AM, Gaucher JF, Burlacu-Miron S, Sakamoto H, Janin J, Barzu O
TitleStructures of escherichia coli CMP kinase alone and in complex with CDP: a new fold of the nucleoside monophosphate binding domain and insights into cytosine nucleotide specificity.
Related PDB1cke,2cmk
Related UniProtKBP0A6I0
[8]
PubMed ID10426946
JournalNat Struct Biol
Year1999
Volume6
Pages721-3
AuthorsSchlichting I, Reinstein J
TitlepH influences fluoride coordination number of the AlFx phosphoryl transfer transition state analog.
Related PDB1qf9,5ukd
[9]
PubMed ID10218107
JournalAdv Enzymol Relat Areas Mol Biol
Year1999
Volume73
Pages103-34
AuthorsYan H, Tsai MD
TitleNucleoside monophosphate kinases: structure, mechanism, and substrate specificity.
[10]
PubMed ID11152133
JournalProtein Sci
Year2000
Volume9
Pages2225-31
AuthorsHutter MC, Helms V
TitlePhosphoryl transfer by a concerted reaction mechanism in UMP/CMP-kinase.
[11]
PubMed ID11123913
JournalBiochemistry
Year2000
Volume39
Pages15870-8
AuthorsLi de La Sierra IM, Gallay J, Vincent M, Bertrand T, Briozzo P, Barzu O, Gilles AM
TitleSubstrate-induced fit of the ATP binding site of cytidine monophosphate kinase from Escherichia coli: time-resolved fluorescence of 3'-anthraniloyl-2'-deoxy-ADP and molecular modeling.
[12]
PubMed ID11827479
JournalJ Mol Biol
Year2002
Volume315
Pages1099-110
AuthorsBertrand T, Briozzo P, Assairi L, Ofiteru A, Bucurenci N, Munier-Lehmann H, Golinelli-Pimpaneau B, Barzu O, Gilles AM
TitleSugar specificity of bacterial CMP kinases as revealed by crystal structures and mutagenesis of Escherichia coli enzyme.
[13]
PubMed ID15163660
JournalJ Biol Chem
Year2004
Volume279
Pages33882-9
AuthorsSegura-Pena D, Sekulic N, Ort S, Konrad M, Lavie A
TitleSubstrate-induced conformational changes in human UMP/CMP kinase.
Related PDB1tev

comments
Literature [6] concluded that the mechanism of phosphoryl transfer has a strong associative character rather than dissociative character.
According to the literature [6] & [10], the positions of the catalytic Mg2+ ion and the conserved lysine residue, Lys19, of the P-loop are invariant during the reaction, suggesting that they just provide a structural template for phosphoryl transfer. In contrast, catalytic arginine residues move to stabilize negative charges that develop during the reaction [6].
The paper [10] proposed a concerted reaction mechanism, in which a proton shifts synchronously from the monophosphate of the acceptor substrate to the transferred phosphate group.

createdupdated
2002-05-312010-05-24


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