EzCatDB: S00808
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DB codeS00808
RLCP classification4.12.642300.465 : Addition
5.201.1660000.464 : Elimination
CATH domainDomain 13.40.140.10 : Cytidine Deaminase; domain 2Catalytic domain
E.C.3.5.4.12

CATH domainRelated DB codes (homologues)
3.40.140.10 : Cytidine Deaminase; domain 2S00810,D00406

Enzyme Name
UniProtKBKEGG

P16006Q8DSE5
Protein nameDeoxycytidylate deaminase
dCMP deaminase
Deoxycytidylate deaminase
Deoxy-CMP-deaminase
Deoxycytidylate aminohydrolase
Deoxycytidine monophosphate deaminase
Deoxycytidine-5'-phosphate deaminase
Deoxycytidine-5'-monophosphate aminohydrolase
SynonymsEC 3.5.4.12
dCMP deaminase
dCD
Putative deoxycytidylate deaminase
RefSeqNP_049828.1 (Protein)
NC_000866.4 (DNA/RNA sequence)
NP_722165.1 (Protein)
NC_004350.2 (DNA/RNA sequence)
PfamPF00383 (dCMP_cyt_deam_1)
[Graphical view]
PF00383 (dCMP_cyt_deam_1)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00240Pyrimidine metabolism
MAP03090Type II secretion system

UniProtKB:Accession NumberP16006Q8DSE5
Entry nameDCTD_BPT4Q8DSE5_STRMU
ActivitydCMP + H(2)O = dUMP + NH(3).
SubunitHomohexamer.
Subcellular location

CofactorBinds 2 zinc ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00038C00239C00001C00365C00014I00056
CompoundZincdCMPH2OdUMPNH34-hydroxy-deoxycytidine monophosphate
Typeheavy metalamine group,nucleotideH2Oamide group,nucleotideamine group,organic ion
ChEBI29105
15918
15377
17622
16134

PubChem32051
13945
962
22247451
65063
222

              
1vq2A00Bound:2x_ZNUnbound UnboundUnboundTransition-state-analogue:DDN
1teoA00Bound:2x_ZNUnbound UnboundUnboundTransition-state-analogue:_DU
2hvvA00Bound:2x_ZNUnbound UnboundUnboundUnbound
2hvvB00Bound:2x_ZNUnbound UnboundUnboundUnbound
2hvwA00Bound:2x_ZNUnbound UnboundUnboundTransition-state-analogue:DDN
2hvwB00Bound:2x_ZNUnbound UnboundUnboundTransition-state-analogue:DDN
2hvwC00Bound:2x_ZNUnbound UnboundUnboundTransition-state-analogue:DDN

Active-site residues
resource
PDB;1vq2 & literature [7], [11], [12]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1vq2A00GLU 106
HIS 104;CYS 132;CYS 135(Catalytic zinc)
SER 130
mutant R115E
1teoA00GLU 106
HIS 104;CYS 132;CYS 135(Catalytic zinc)
SER 130
mutant R115E
2hvvA00GLU  73
HIS  71;CYS  99;CYS 102(Catalytic zinc)
PHE  97
 
2hvvB00GLU  73
HIS  71;CYS  99;CYS 102(Catalytic zinc)
PHE  97
 
2hvwA00GLU  73
HIS  71;CYS  99;CYS 102(Catalytic zinc)
PHE  97
 
2hvwB00GLU  73
HIS  71;CYS  99;CYS 102(Catalytic zinc)
PHE  97
 
2hvwC00GLU  73
HIS  71;CYS  99;CYS 102(Catalytic zinc)
PHE  97
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]Fig. 12, p. 651-653
[11]

[12]p. 228-229

references
[1]
PubMed ID7120402
JournalJ Mol Biol
Year1982
Volume157
Pages557-70
AuthorsRaia CA, Nucci R, Vaccaro C, Sepe S, Rella R, Rossi M
TitleReversal of the effect of the allosteric ligands of dCMP-aminohydrolase and stabilization of the enzyme in the T form.
[2]
PubMed ID3110545
JournalMethods Enzymol
Year1987
Volume135
Pages577-85
AuthorsRossi M, Raia CA, Vaccaro C
TitleChemical stabilization of conformational states of dCMP deaminase.
[3]
PubMed ID1898061
JournalArch Biochem Biophys
Year1991
Volume289
Pages19-25
AuthorsNucci R, Raia CA, Vaccaro C, Rossi M, Whitehead EP
TitleAllosteric modifier and substrate binding of donkey deoxycytidylate aminohydrolase (EC 3.5.4.12).
[4]
PubMed ID8448179
JournalBiochim Biophys Acta
Year1993
Volume1162
Pages161-70
AuthorsMaley GF, Lobo AP, Maley F
TitleProperties of an affinity-column-purified human deoxycytidylate deaminase.
[5]
PubMed ID8428902
JournalJ Biol Chem
Year1993
Volume268
Pages2288-91
AuthorsMoore JT, Silversmith RE, Maley GF, Maley F
TitleT4-phage deoxycytidylate deaminase is a metalloprotein containing two zinc atoms per subunit.
Related UniProtKBP16006
[6]
PubMed ID8117667
JournalBiochemistry
Year1994
Volume33
Pages2104-12
AuthorsMoore JT, Cie?la JM, Changchien LM, Maley GF, Maley F
TitleIdentification of a site necessary for allosteric regulation in T4-phage deoxycytidylate deaminase.
[7]
PubMed ID8289286
JournalJ Mol Biol
Year1994
Volume235
Pages635-56
AuthorsBetts L, Xiang S, Short SA, Wolfenden R, Carter CW Jr
TitleCytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex.
[8]
PubMed ID8798492
JournalJ Biol Chem
Year1996
Volume271
Pages23037-42
AuthorsMcGaughey KM, Wheeler LJ, Moore JT, Maley GF, Maley F, Mathews CK
TitleProtein-protein interactions involving T4 phage-coded deoxycytidylate deaminase and thymidylate synthase.
[9]
PubMed ID10026292
JournalBiochemistry
Year1999
Volume38
Pages2094-101
AuthorsHazebrouck S, Maley F, Machtelinckx V, Sonigo P, Kupiec JJ
TitleStructural and functional analysis of surface domains unique to bacteriophage T4 thymidylate synthase.
[10]
PubMed ID10777550
JournalJ Biol Chem
Year2000
Volume275
Pages12598-602
AuthorsKeefe RG, Maley GF, Saxl RL, Maley F
TitleA T4-phage deoxycytidylate deaminase mutant that no longer requires deoxycytidine 5'-triphosphate for activation.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLU-115 IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS.
PubMed ID15504034
JournalBiochemistry
Year2004
Volume43
Pages13715-23
AuthorsAlmog R, Maley F, Maley GF, Maccoll R, Van Roey P
TitleThree-dimensional structure of the R115E mutant of T4-bacteriophage 2'-deoxycytidylate deaminase.
Related PDB1vq2,1teo
Related UniProtKBP16006
[12]
PubMed ID18255096
JournalJ Mol Biol
Year2008
Volume377
Pages220-31
AuthorsHou HF, Liang YH, Li LF, Su XD, Dong YH
TitleCrystal structures of Streptococcus mutans 2'-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dCTP x Mg2+.

comments
This is an allosteric enzyme, but the manner in which dCTP (activator) and dTTP (inhibitor) regulate dCMP deaminase activity remains unclear. 2hvw of PDB bindss dCTP molecules as regulators, as well as the transition-state-analogue.
Considering the active site of this enzyme, and the catalytic domain structure, this enzyme is homologous to cytidine deaminase (D00406 in EzCatDB), with the same catalytic mechanism.
Although this enzyme binds two zinc ions, only one zinc is involved in catalysis.
This enzyme also catalyzes two successive reactions (rather than hydrolysis) as follows:
(A) Addition of water to imine carbon to form a tetrahedral intermediate.
(B) Elimination of amine group from the intermediate, forming a carbonyl group. Although carbonyl oxygen of Thr acts as a stabilizer for the leaving amine group in cytidine deaminase (D00406 in EzCatDB), this enzyme adopts different residues, which are similarly located as the Thr residue. The enzyme from Bacteriophage T4 uses the carbonyl group of Ser130, whereas the counterpart from Bacteria, Streptococcus mutans, uses that of Phe97.

createdupdated
2008-09-192012-10-16


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