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MetaCyc Enzyme: cytidine deaminase

Gene: cdd Accession Numbers: EG10137 (MetaCyc), b2143, ECK2136

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of cytidine deaminase = [Cdd]2

Summary:
Cytidine deaminase catalyzes the hydrolytic deamination of cytidine and 2'-deoxycytidine to uridine and 2'-deoxyuridine, respectively, in a thermodynamically favorable reaction. 2'-deoxycytidine is a better substrate than cytidine [Ashley84]. The products can undergo phosphorolysis to yield pentose derivatives. This allows cytidine to serve as a sole carbon source [HammerJespersen73].

Crystal structures of the enzyme have been solved, contributing to the understanding of the catalytic mechanism [Betts89, Betts94, Shih96]. Kinetic analysis showed a rapid-equilibrium random uni-bi mechanism [Vita85]. The catalytic mechanism of cytidine deaminase has been studied [Frick89, Carlow95, Carlow96, Xiang96, Carlow98, Carlow98a, Snider00, Snider01, Snider02, Snider02a, Noonan02, Borchers04, Rao05]. The enzyme binds one atom of zinc per subunit [Yang92]; the zinc-binding motif has been identified [Reizer94b]. Site-directed mutagenesis of the zinc-liganding cysteine residues results in loss of zinc and dramatic reduction in enzymatic activity [Smith94b].

Expression of cdd is induced by cytosine [Josephsen81] and oleic acid [Han08b]. Expression is downregulated in an iscS mutant [Mihara08].

Review: [Carter95]

Citations: [Josephsen83, Middendorf84]

Locations: cytosol

Map Position: [2,229,866 -> 2,230,750]

Molecular Weight of Polypeptide: 31.54 kD (from nucleotide sequence), 35.0 kD (experimental) [Ashley84 ]

Molecular Weight of Multimer: 54.0 kD (experimental) [Hosono73]

pI: 5.74

Unification Links: ASAP:ABE-0007086 , CGSC:932 , DIP:DIP-36169N , EchoBASE:EB0135 , EcoGene:EG10137 , EcoliWiki:b2143 , Mint:MINT-1283574 , ModBase:P0ABF6 , OU-Microarray:b2143 , PortEco:cdd , Pride:P0ABF6 , Protein Model Portal:P0ABF6 , RefSeq:NP_416648 , RegulonDB:EG10137 , SMR:P0ABF6 , String:511145.b2143 , UniProt:P0ABF6

Relationship Links: InterPro:IN-FAMILY:IPR002125 , InterPro:IN-FAMILY:IPR006263 , InterPro:IN-FAMILY:IPR013171 , InterPro:IN-FAMILY:IPR016192 , InterPro:IN-FAMILY:IPR016193 , InterPro:IN-FAMILY:IPR020797 , Panther:IN-FAMILY:PTHR11644:SF12 , PDB:Structure:1AF2 , PDB:Structure:1ALN , PDB:Structure:1CTT , PDB:Structure:1CTU , Pfam:IN-FAMILY:PF00383 , Pfam:IN-FAMILY:PF08211 , Prosite:IN-FAMILY:PS00903

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006217 - deoxycytidine catabolic process Inferred from experiment [Ashley84]
GO:0009972 - cytidine deamination Inferred from experiment Inferred by computational analysis [GOA01a, HammerJespersen73]
GO:0015949 - nucleobase-containing small molecule interconversion Inferred from experiment [Cohen71, Cohen71a]
Molecular Function: GO:0001884 - pyrimidine nucleoside binding Inferred from experiment [Vita85]
GO:0004126 - cytidine deaminase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Betts89, Cohen71a]
GO:0008270 - zinc ion binding Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Yang92, Betts94]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Lasserre06]
GO:0042803 - protein homodimerization activity Inferred from experiment [Hosono73]
GO:0047844 - deoxycytidine deaminase activity Inferred from experiment [Ashley84]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ishihama08, MunchPetersen76, Lasserre06]

MultiFun Terms: metabolism central intermediary metabolism nucleotide and nucleoside conversions

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: cytidine deaminase

Synonyms: CDase, CDA, cytidine aminohydrolase

EC Number: 3.5.4.5

cytidine + H+ + H2O <=> uridine + ammonium

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for cytidine: 5-methylcytidine [Vita85 ] , N4-aminocytidine [Negishi88 ]

In Pathways: superpathway of pyrimidine ribonucleosides salvage , pyrimidine ribonucleosides salvage II , pyrimidine ribonucleosides degradation , pyrimidine ribonucleosides salvage I

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The enzyme was first detected in E. coli strain 15 [Wang50] and characterized from E. coli B [Cohen71a, Cohen71, Evans75, Ashley82, Ashley84]. The sequences of the E. coli K-12 and B REL606 enzymes are 100% identical.

Citations: [Ashley84a]

Cofactors or Prosthetic Groups: Zn2+ [Yang92]

Inhibitors (Competitive): pyrimidin-2-one-ribonucleoside (Kic = 0.36µM) [Frick89] , 5-fluoropyrimidin-2-one-ribonucleoside (Kic = 0.035µM) [Frick89]

Kinetic Parameters:

Substrate
Km (μM)
Citations
cytidine
220.0
[Ashley84]

pH(opt): 6-7.5 [Hosono73]


Enzymatic reaction of: deoxycytidine deaminase

Synonyms: deoxycytidine aminohydrolase

EC Number: 3.5.4.5

2'-deoxycytidine + H+ + H2O <=> 2'-deoxyuridine + ammonium

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of pyrimidine deoxyribonucleosides degradation , pyrimidine deoxyribonucleosides degradation

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Cofactors or Prosthetic Groups: Zn2+ [Yang92]

Inhibitors (Unknown Mechanism): 5-(chloromercuri)cytidine [Ashley84]

Kinetic Parameters:

Substrate
Km (μM)
Citations
2'-deoxycytidine
58.0
[Ashley84]


Sequence Features

Feature Class Location Citations Comment
Sequence-Conflict 4
[GonzalezGil96, UniProt10]
Alternate sequence: I; UniProt: (in Ref. 9; AA sequence);
Conserved-Region 56 -> 139
[UniProt13]
UniProt: CMP/dCMP deaminase zinc-binding.
Sequence-Conflict 58 -> 77
[ValentinHansen89, UniProt10]
Alternate sequence: RWRRPVRVRHCRILMLAQLR; UniProt: (in Ref. 6);
Protein-Segment 89 -> 91
[UniProt10a]
UniProt: Substrate binding; Sequence Annotation Type: region of interest;
Metal-Binding-Site 102
[UniProt10]
UniProt: Zinc; catalytic;
Active-Site 104
[UniProt10]
UniProt: Proton donor;
Metal-Binding-Site 129
[UniProt10]
UniProt: Zinc; catalytic;
Metal-Binding-Site 132
[UniProt10]
UniProt: Zinc; catalytic;

History:
10/20/97 Gene b2143 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10137; confirmed by SwissProt match.


References

Ashley82: Ashley GW, Bartlett PA (1982). "A phosphorus-containing pyrimidine analog as a potent inhibitor of cytidine deaminase." Biochem Biophys Res Commun 108(4);1467-74. PMID: 6758781

Ashley84: Ashley GW, Bartlett PA (1984). "Purification and properties of cytidine deaminase from escherichia coli." J Biol Chem 1984;259(21);13615-20. PMID: 6386817

Ashley84a: Ashley GW, Bartlett PA (1984). "Inhibition of Escherichia coli cytidine deaminase by a phosphapyrimidine nucleoside." J Biol Chem 259(21);13621-7. PMID: 6386818

Betts89: Betts L, Frick L, Wolfenden R, Carter CW (1989). "Incomplete factorial search for conditions leading to high quality crystals of Escherichia coli cytidine deaminase complexed to a transition state analog inhibitor." J Biol Chem 1989;264(12);6737-40. PMID: 2651432

Betts94: Betts L, Xiang S, Short SA, Wolfenden R, Carter CW (1994). "Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex." J Mol Biol 235(2);635-56. PMID: 8289286

Borchers04: Borchers CH, Marquez VE, Schroeder GK, Short SA, Snider MJ, Speir JP, Wolfenden R (2004). "Fourier transform ion cyclotron resonance MS reveals the presence of a water molecule in an enzyme transition-state analogue complex." Proc Natl Acad Sci U S A 101(43);15341-5. PMID: 15494437

Carlow95: Carlow DC, Smith AA, Yang CC, Short SA, Wolfenden R (1995). "Major contribution of a carboxymethyl group to transition-state stabilization by cytidine deaminase: mutation and rescue." Biochemistry 1995;34(13);4220-4. PMID: 7703234

Carlow96: Carlow DC, Short SA, Wolfenden R (1996). "Role of glutamate-104 in generating a transition state analogue inhibitor at the active site of cytidine deaminase." Biochemistry 35(3);948-54. PMID: 8547277

Carlow98: Carlow DC, Short SA, Wolfenden R (1998). "Complementary truncations of a hydrogen bond to ribose involved in transition-state stabilization by cytidine deaminase." Biochemistry 37(5);1199-203. PMID: 9477944

Carlow98a: Carlow D, Wolfenden R (1998). "Substrate connectivity effects in the transition state for cytidine deaminase." Biochemistry 37(34);11873-8. PMID: 9718310

Carlow99: Carlow DC, Carter CW, Mejlhede N, Neuhard J, Wolfenden R (1999). "Cytidine deaminases from B. subtilis and E. coli: compensating effects of changing zinc coordination and quaternary structure." Biochemistry 38(38);12258-65. PMID: 10493793

Carter95: Carter CW (1995). "The nucleoside deaminases for cytidine and adenosine: structure, transition state stabilization, mechanism, and evolution." Biochimie 77(1-2);92-8. PMID: 7599282

Cohen71: Cohen RM, Wolfenden R (1971). "The equilibrium of hydrolytic deamination of cytidine and N 4 -methylcytidine." J Biol Chem 246(24);7566-8. PMID: 4944312

Cohen71a: Cohen RM, Wolfenden R (1971). "Cytidine deaminase from Escherichia coli. Purification, properties and inhibition by the potential transition state analog 3,4,5,6-tetrahydrouridine." J Biol Chem 246(24);7561-5. PMID: 4944311

Evans75: Evans BE, Mitchell GN, Wolfenden R (1975). "The action of bacterial cytidine deaminase on 5,6-dihydrocytidine." Biochemistry 14(3);621-4. PMID: 1090298

Frick89: Frick L, Yang C, Marquez VE, Wolfenden R (1989). "Binding of pyrimidin-2-one ribonucleoside by cytidine deaminase as the transition-state analogue 3,4-dihydrouridine and the contribution of the 4-hydroxyl group to its binding affinity." Biochemistry 1989;28(24);9423-30. PMID: 2692708

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

GonzalezGil96: Gonzalez-Gil G, Bringmann P, Kahmann R (1996). "FIS is a regulator of metabolism in Escherichia coli." Mol Microbiol 22(1);21-9. PMID: 8899705

HammerJespersen73: Hammer-Jespersen K, Munch-Petersen A (1973). "Mutants of Escherichia coli unable to metabolize cytidine: isolation and characterization." Mol Gen Genet 126(2);177-86. PMID: 4360102

Han08b: Han MJ, Lee JW, Lee SY, Yoo JS (2008). "Proteome-level responses of Escherichia coli to long-chain fatty acids and use of fatty acid inducible promoter in protein production." J Biomed Biotechnol 2008;735101. PMID: 18317523

Hosono73: Hosono H, Kuno S (1973). "The purification and properties of cytidine deaminase from Escherichia coli." J Biochem 74(4);797-803. PMID: 4202859

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Josephsen81: Josephsen J, Hammer-Jespersen K (1981). "Fusion of the lac genes to the promotor for the cytidine deaminase gene of Escherichia coli K-12." Mol Gen Genet 182(1);154-8. PMID: 6455590

Josephsen83: Josephsen J, Hammer-Jespersen K, Hansen TD (1983). "Mapping of the gene for cytidine deaminase (cdd) in Escherichia coli K-12." J Bacteriol 154(1);72-5. PMID: 6339482

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Middendorf84: Middendorf A, Schweizer H, Vreemann J, Boos W (1984). "Mapping of markers in the gyrA-his region of Escherichia coli." Mol Gen Genet 197(1);175-81. PMID: 6392823

Mihara08: Mihara H, Hidese R, Yamane M, Kurihara T, Esaki N (2008). "The iscS gene deficiency affects the expression of pyrimidine metabolism genes." Biochem Biophys Res Commun 372(3);407-11. PMID: 18482579

MunchPetersen76: Munch-Petersen A, Mygind B (1976). "Nucleoside transport systems in Escherichia coli K12: specificity and regulation." J Cell Physiol 89(4);551-9. PMID: 827549

Negishi88: Negishi K, Tamanoi K, Ishii M, Kawakami M, Yamashita Y, Hayatsu H (1988). "Mutagenic nucleoside analog N4-aminocytidine: metabolism, incorporation into DNA, and mutagenesis in Escherichia coli." J Bacteriol 170(11);5257-62. PMID: 3053653

Noonan02: Noonan RC, Carter CW CW, Bagdassarian CK (2002). "Enzymatic conformational fluctuations along the reaction coordinate of cytidine deaminase." Protein Sci 11(6);1424-34. PMID: 12021441

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Rao05: Rao N, Xu Q, Guo H (2005). "Origin of tight binding of a near-perfect transition-state analogue by cytidine deaminase: implications for enzyme catalysis." J Am Chem Soc 127(9);3191-7. PMID: 15740159

Reizer94b: Reizer J, Buskirk S, Bairoch A, Reizer A, Saier MH (1994). "A novel zinc-binding motif found in two ubiquitous deaminase families." Protein Sci 3(5);853-6. PMID: 8061614

Shih96: Shih P, Wolfenden R (1996). "Enzyme-substrate complexes of adenosine and cytidine deaminases: absence of accumulation of water adducts." Biochemistry 35(15);4697-703. PMID: 8664259

Smith94b: Smith AA, Carlow DC, Wolfenden R, Short SA (1994). "Mutations affecting transition-state stabilization by residues coordinating zinc at the active site of cytidine deaminase." Biochemistry 33(21);6468-74. PMID: 8204580

Snider00: Snider MJ, Gaunitz S, Ridgway C, Short SA, Wolfenden R (2000). "Temperature effects on the catalytic efficiency, rate enhancement, and transition state affinity of cytidine deaminase, and the thermodynamic consequences for catalysis of removing a substrate "anchor"." Biochemistry 39(32);9746-53. PMID: 10933791

Snider01: Snider MJ, Wolfenden R (2001). "Site-bound water and the shortcomings of a less than perfect transition state analogue." Biochemistry 40(38);11364-71. PMID: 11560484

Snider02: Snider MJ, Reinhardt L, Wolfenden R, Cleland WW (2002). "15N kinetic isotope effects on uncatalyzed and enzymatic deamination of cytidine." Biochemistry 41(1);415-21. PMID: 11772041

Snider02a: Snider MJ, Lazarevic D, Wolfenden R (2002). "Catalysis by entropic effects: the action of cytidine deaminase on 5,6-dihydrocytidine." Biochemistry 41(12);3925-30. PMID: 11900535

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

ValentinHansen89: Valentin-Hansen P, Holst B, Josephsen J, Hammer K, Albrechtsen B (1989). "CRP/cAMP- and CytR-regulated promoters in Escherichia coli K12: the cdd promoter." Mol Microbiol 3(10);1385-90. PMID: 2575702

Vita85: Vita A, Amici A, Cacciamani T, Lanciotti M, Magni G (1985). "Cytidine deaminase from Escherichia coli B. Purification and enzymatic and molecular properties." Biochemistry 24(21);6020-4. PMID: 3910086

Wang50: Wang TP, Sable HZ, Lampen JO (1950). "Enzymatic deamination of cytosine nucleosides." J Biol Chem 184(1);17-28. PMID: 15421968

Xiang96: Xiang S, Short SA, Wolfenden R, Carter CW (1996). "Cytidine deaminase complexed to 3-deazacytidine: a "valence buffer" in zinc enzyme catalysis." Biochemistry 35(5);1335-41. PMID: 8634261

Yang92: Yang C, Carlow D, Wolfenden R, Short SA (1992). "Cloning and nucleotide sequence of the Escherichia coli cytidine deaminase (ccd) gene." Biochemistry 1992;31(17);4168-74. PMID: 1567863


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, biocyc13.