DB code: S00808

RLCP classification 5.201.1660000.464 : Elimination
4.12.642300.465 : Addition
CATH domain 3.40.140.10 : Cytidine Deaminase; domain 2 Catalytic domain
E.C. 3.5.4.12
CSA
M-CSA
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P16006 Deoxycytidylate deaminase
EC 3.5.4.12
dCMP deaminase
dCD
NP_049828.1 (Protein)
NC_000866.4 (DNA/RNA sequence)
PF00383 (dCMP_cyt_deam_1)
[Graphical View]
Q8DSE5
Putative deoxycytidylate deaminase
NP_722165.1 (Protein)
NC_004350.2 (DNA/RNA sequence)
PF00383 (dCMP_cyt_deam_1)
[Graphical View]

KEGG enzyme name
dCMP deaminase
Deoxycytidylate deaminase
Deoxy-CMP-deaminase
Deoxycytidylate aminohydrolase
Deoxycytidine monophosphate deaminase
Deoxycytidine-5'-phosphate deaminase
Deoxycytidine-5'-monophosphate aminohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q8DSE5 Q8DSE5_STRMU
P16006 DCTD_BPT4 dCMP + H(2)O = dUMP + NH(3). Homohexamer. Binds 2 zinc ions per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP03090 Type II secretion system
MAP00240 Pyrimidine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00239 C00001 C00365 C00014 I00056
E.C.
Compound Zinc dCMP H2O dUMP NH3 4-hydroxy-deoxycytidine monophosphate
Type heavy metal amine group,nucleotide H2O amide group,nucleotide amine group,organic ion
ChEBI 29105
15918
15377
17622
16134
PubChem 32051
13945
22247451
962
65063
222
1vq2A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Transition-state-analogue:DDN
1teoA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Transition-state-analogue:_DU
2hvvA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Unbound
2hvvB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Unbound
2hvwA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Transition-state-analogue:DDN
2hvwB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Transition-state-analogue:DDN
2hvwC00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Transition-state-analogue:DDN

Reference for Active-site residues
resource references E.C.
PDB;1vq2 & literature [7], [11], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1vq2A00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 106 HIS 104;CYS 132;CYS 135(Catalytic zinc) SER 130 mutant R115E
1teoA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 106 HIS 104;CYS 132;CYS 135(Catalytic zinc) SER 130 mutant R115E
2hvvA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 73 HIS 71;CYS 99;CYS 102(Catalytic zinc) PHE 97
2hvvB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 73 HIS 71;CYS 99;CYS 102(Catalytic zinc) PHE 97
2hvwA00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 73 HIS 71;CYS 99;CYS 102(Catalytic zinc) PHE 97
2hvwB00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 73 HIS 71;CYS 99;CYS 102(Catalytic zinc) PHE 97
2hvwC00 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 73 HIS 71;CYS 99;CYS 102(Catalytic zinc) PHE 97

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
Fig. 12, p. 651-653
[11]
[12]
p. 228-229

References
[1]
Resource
Comments
Medline ID
PubMed ID 7120402
Journal J Mol Biol
Year 1982
Volume 157
Pages 557-70
Authors Raia CA, Nucci R, Vaccaro C, Sepe S, Rella R, Rossi M
Title Reversal of the effect of the allosteric ligands of dCMP-aminohydrolase and stabilization of the enzyme in the T form.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3110545
Journal Methods Enzymol
Year 1987
Volume 135
Pages 577-85
Authors Rossi M, Raia CA, Vaccaro C
Title Chemical stabilization of conformational states of dCMP deaminase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1898061
Journal Arch Biochem Biophys
Year 1991
Volume 289
Pages 19-25
Authors Nucci R, Raia CA, Vaccaro C, Rossi M, Whitehead EP
Title Allosteric modifier and substrate binding of donkey deoxycytidylate aminohydrolase (EC 3.5.4.12).
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8448179
Journal Biochim Biophys Acta
Year 1993
Volume 1162
Pages 161-70
Authors Maley GF, Lobo AP, Maley F
Title Properties of an affinity-column-purified human deoxycytidylate deaminase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8428902
Journal J Biol Chem
Year 1993
Volume 268
Pages 2288-91
Authors Moore JT, Silversmith RE, Maley GF, Maley F
Title T4-phage deoxycytidylate deaminase is a metalloprotein containing two zinc atoms per subunit.
Related PDB
Related UniProtKB P16006
[6]
Resource
Comments
Medline ID
PubMed ID 8117667
Journal Biochemistry
Year 1994
Volume 33
Pages 2104-12
Authors Moore JT, Cie?la JM, Changchien LM, Maley GF, Maley F
Title Identification of a site necessary for allosteric regulation in T4-phage deoxycytidylate deaminase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8289286
Journal J Mol Biol
Year 1994
Volume 235
Pages 635-56
Authors Betts L, Xiang S, Short SA, Wolfenden R, Carter CW Jr
Title Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8798492
Journal J Biol Chem
Year 1996
Volume 271
Pages 23037-42
Authors McGaughey KM, Wheeler LJ, Moore JT, Maley GF, Maley F, Mathews CK
Title Protein-protein interactions involving T4 phage-coded deoxycytidylate deaminase and thymidylate synthase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10026292
Journal Biochemistry
Year 1999
Volume 38
Pages 2094-101
Authors Hazebrouck S, Maley F, Machtelinckx V, Sonigo P, Kupiec JJ
Title Structural and functional analysis of surface domains unique to bacteriophage T4 thymidylate synthase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10777550
Journal J Biol Chem
Year 2000
Volume 275
Pages 12598-602
Authors Keefe RG, Maley GF, Saxl RL, Maley F
Title A T4-phage deoxycytidylate deaminase mutant that no longer requires deoxycytidine 5'-triphosphate for activation.
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT GLU-115 IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS.
Medline ID
PubMed ID 15504034
Journal Biochemistry
Year 2004
Volume 43
Pages 13715-23
Authors Almog R, Maley F, Maley GF, Maccoll R, Van Roey P
Title Three-dimensional structure of the R115E mutant of T4-bacteriophage 2'-deoxycytidylate deaminase.
Related PDB 1vq2 1teo
Related UniProtKB P16006
[12]
Resource
Comments
Medline ID
PubMed ID 18255096
Journal J Mol Biol
Year 2008
Volume 377
Pages 220-31
Authors Hou HF, Liang YH, Li LF, Su XD, Dong YH
Title Crystal structures of Streptococcus mutans 2'-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dCTP x Mg2+.
Related PDB
Related UniProtKB

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.

Created Updated
2008-09-19 2012-10-16