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Escherichia coli K-12 substr. MG1655 Enzyme: dCTP deaminase



Gene: dcd Accession Numbers: EG11418 (EcoCyc), b2065, ECK2059

Synonyms: dus, paxA

Regulation Summary Diagram: ?

Subunit composition of dCTP deaminase = [Dcd]3

Summary:
This enzyme catalyzes the deamination of dCTP to dUTP in the main pathway for dTTP biosynthesis in Escherichia coli and Salmonella enterica serovar Typhimurium. This enzyme is unusual among nucleoside and nucleotide deaminases in that it does not require a metal ion for catalysis. The crystal structures of wild-type and mutant forms of the enzyme from E. coli K-12 have been determined and a catalytic mechanism proposed. The enzyme has been determined to be a homotrimer [Johansson05, Thymark08, Johansson07].

Gene Citations: [Neuhard76]

Locations: cytosol

Map Position: [2,139,658 <- 2,140,239] (46.12 centisomes)
Length: 582 bp / 193 aa

Molecular Weight of Polypeptide: 21.249 kD (from nucleotide sequence)

pI: 5.92

Unification Links: ASAP:ABE-0006835 , CGSC:875 , EchoBASE:EB1389 , EcoGene:EG11418 , EcoliWiki:b2065 , ModBase:P28248 , OU-Microarray:b2065 , PortEco:dcd , PR:PRO_000022406 , Pride:P28248 , Protein Model Portal:P28248 , RefSeq:NP_416569 , RegulonDB:EG11418 , SMR:P28248 , String:511145.b2065 , UniProt:P28248

Relationship Links: InterPro:IN-FAMILY:IPR008180 , InterPro:IN-FAMILY:IPR011962 , PDB:Structure:1XS1 , PDB:Structure:1XS4 , PDB:Structure:1XS6 , PDB:Structure:2J4H , PDB:Structure:2J4Q , PDB:Structure:2V9X , Pfam:IN-FAMILY:PF00692

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0015949 - nucleobase-containing small molecule interconversion Inferred from experiment [ODonovan71]
GO:0006226 - dUMP biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0006229 - dUTP biosynthetic process Inferred by computational analysis [GOA01]
GO:0009117 - nucleotide metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0009220 - pyrimidine ribonucleotide biosynthetic process Inferred by computational analysis [GOA06]
GO:0046080 - dUTP metabolic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0008829 - dCTP deaminase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, ODonovan71, Johansson05]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11, GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: metabolism central intermediary metabolism nucleotide and nucleoside conversions

Essentiality data for dcd knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 24-Mar-2008 by Fulcher C , SRI International


Enzymatic reaction of: dCTP deaminase

Synonyms: deoxycytidine triphosphate deaminase, dCTP aminohydrolase

EC Number: 3.5.4.13

dCTP + H+ + H2O <=> ammonium + dUTP

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 irreversible in the direction shown.

In Pathways: superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli) , pyrimidine deoxyribonucleotides de novo biosynthesis II

Summary:
dCTP deaminase catalyzes a reaction that supplies deoxyuridine monphosphate, the substrate for thymidylate synthetase. This represents a second pathway for dUMP and subsequently dTMP biosynthesis. [ODonovan71] Under aerobic conditions 75% of dUTP is produced by dCTP deaminase. [Weiss94]

The enzyme from Salmonella enterica serovar Typhimurium has been shown to be inhibited by dTTP and dUTP [Beck75].

Inhibitors (Unknown Mechanism): phosphate [Johansson05] , dUTP , dTTP [Johansson07]

Primary Physiological Regulators of Enzyme Activity: dUTP , dTTP

Kinetic Parameters:

Substrate
kcat (sec-1)
Citations
dCTP
1.24
[Thymark08, BRENDA14]


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b2065 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11418; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Beck75: Beck CF, Eisenhardt AR, Neuhard J (1975). "Deoxycytidine triphosphate deaminase of Salmonella typhimurium. Purification and characterization." J Biol Chem 250(2);609-16. PMID: 234434

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

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

Johansson05: Johansson E, Fano M, Bynck JH, Neuhard J, Larsen S, Sigurskjold BW, Christensen U, Willemoes M (2005). "Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes." J Biol Chem 280(4);3051-9. PMID: 15539408

Johansson07: Johansson E, Thymark M, Bynck JH, Fano M, Larsen S, Willemoes M (2007). "Regulation of dCTP deaminase from Escherichia coli by nonallosteric dTTP binding to an inactive form of the enzyme." FEBS J 274(16);4188-98. PMID: 17651436

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Neuhard76: Neuhard J, Thomassen E (1976). "Altered deoxyribonucleotide pools in P2 eductants of Escherichia coli K-12 due to deletion of the dcd gene." J Bacteriol 1976;126(2);999-1001. PMID: 177407

ODonovan71: O'Donovan GA, Edlin G, Fuchs JA, Neuhard J, Thomassen E (1971). "Deoxycytidine triphosphate deaminase: characterization of an Escherichia coli mutant deficient in the enzyme." J Bacteriol 1971;105(2);666-72. PMID: 5541540

Thymark08: Thymark M, Johansson E, Larsen S, Willemoes M (2008). "Mutational analysis of the nucleotide binding site of Escherichia coli dCTP deaminase." Arch Biochem Biophys 470(1);20-6. PMID: 17996716

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Weiss94: Weiss B, Wang L (1994). "De novo synthesis of thymidylate via deoxycytidine in dcd (dCTP deaminase) mutants of Escherichia coli." J Bacteriol 1994;176(8);2194-9. PMID: 8157589

Other References Related to Gene Regulation

Shimada13a: Shimada T, Kori A, Ishihama A (2013). "Involvement of the ribose operon repressor RbsR in regulation of purine nucleotide synthesis in Escherichia coli." FEMS Microbiol Lett 344(2);159-65. PMID: 23651393

Zaslaver06: Zaslaver A, Bren A, Ronen M, Itzkovitz S, Kikoin I, Shavit S, Liebermeister W, Surette MG, Alon U (2006). "A comprehensive library of fluorescent transcriptional reporters for Escherichia coli." Nat Methods 3(8);623-8. PMID: 16862137


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, BIOCYC13B.