Cytosine deaminase

Details

Name
Cytosine deaminase
Synonyms
  • 3.5.4.1
  • CD
  • Cytosine aminohydrolase
  • Isoguanine deaminase
Gene Name
codA
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0003689|Cytosine deaminase
MSNNALQTIINARLPGEEGLWQIHLQDGKISAIDAQSGVMPITENSLDAEQGLVIPPFVE
PHIHLDTTQTAGQPNWNQSGTLFEGIERWAERKALLTHDDVKQRAWQTLKWQIANGIQHV
RTHVDVSDATLTALKAMLEVKQEVAPWIDLQIVAFPQEGILSYPNGEALLEEALRLGADV
VGAIPHFEFTREYGVESLHKTFALAQKYDRLIDVHCDEIDDEQSRFVETVAALAHHEGMG
ARVTASHTTAMHSYNGAYTSRLFRLLKMSGINFVANPLVNIHLQGRFDTYPKRRGITRVK
EMLESGINVCFGHDDVFDPWYPLGTANMLQVLHMGLHVCQLMGYGQINDGLNLITHHSAR
TLNLQDYGIAAGNSANLIILPAENGFDALRRQVPVRYSVRGGKVIASTQPAQTTVYLEQP
EAIDYKR
Number of residues
427
Molecular Weight
47590.66
Theoretical pI
6.1
GO Classification
Functions
cytosine deaminase activity / ferrous iron binding / identical protein binding / isoguanine deaminase activity / zinc ion binding
Processes
cytosine catabolic process
Components
cytosol
General Function
Zinc ion binding
Specific Function
Catalyzes the hydrolytic deamination of cytosine to uracil. Is involved in the pyrimidine salvage pathway, which allows the cell to utilize cytosine for pyrimidine nucleotide synthesis. Is also able to catalyze deamination of isoguanine, a mutagenic oxidation product of adenine in DNA, and of isocytosine. To a lesser extent, also catalyzes the conversion of 5-fluorocytosine (5FC) to 5-fluorouracil (5FU); this activity allows the formation of a cytotoxic chemotherapeutic agent from a non-cytotoxic precursor.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0011334|Cytosine deaminase (codA)
GTGTCGAATAACGCTTTACAAACAATTATTAACGCCCGGTTACCAGGCGAAGAGGGGCTG
TGGCAGATTCATCTGCAGGACGGAAAAATCAGCGCCATTGATGCGCAATCCGGCGTGATG
CCCATAACTGAAAACAGCCTGGATGCCGAACAAGGTTTAGTTATACCGCCGTTTGTGGAG
CCACATATTCACCTGGACACCACGCAAACCGCCGGACAACCGAACTGGAATCAGTCCGGC
ACGCTGTTTGAAGGCATTGAACGCTGGGCCGAGCGCAAAGCGTTATTAACCCATGACGAT
GTGAAACAACGCGCATGGCAAACGCTGAAATGGCAGATTGCCAACGGCATTCAGCATGTG
CGTACCCATGTCGATGTTTCGGATGCAACGCTAACTGCGCTGAAAGCAATGCTGGAAGTG
AAGCAGGAAGTCGCGCCGTGGATTGATCTGCAAATCGTCGCCTTCCCTCAGGAAGGGATT
TTGTCGTATCCCAACGGTGAAGCGTTGCTGGAAGAGGCGTTACGCTTAGGGGCAGATGTA
GTGGGGGCGATTCCGCATTTTGAATTTACCCGTGAATACGGCGTGGAGTCGCTGCATAAA
ACCTTCGCCCTGGCGCAAAAATACGACCGTCTCATCGACGTTCACTGTGATGAGATCGAT
GACGAGCAGTCGCGCTTTGTCGAAACCGTTGCTGCCCTGGCGCACCATGAAGGCATGGGC
GCGCGAGTCACCGCCAGCCACACCACGGCAATGCACTCCTATAACGGGGCGTATACCTCA
CGCCTGTTCCGCTTGCTGAAAATGTCCGGTATTAACTTTGTCGCCAACCCGCTGGTCAAT
ATTCATCTGCAAGGACGTTTCGATACGTATCCAAAACGTCGCGGCATCACGCGCGTTAAA
GAGATGCTGGAGTCCGGCATTAACGTCTGCTTTGGTCACGATGATGTCTTCGATCCGTGG
TATCCGCTGGGAACGGCGAATATGCTGCAAGTGCTGCATATGGGGCTGCATGTTTGCCAG
TTGATGGGCTACGGGCAGATTAACGATGGCCTGAATTTAATCACCCACCACAGCGCAAGG
ACGTTGAATTTGCAGGATTACGGCATTGCCGCCGGAAACAGCGCCAACCTGATTATCCTG
CCGGCTGAAAATGGGTTTGATGCGCTGCGCCGTCAGGTTCCGGTACGTTATTCGGTACGT
GGCGGCAAGGTGATTGCCAGCACACAACCGGCACAAACCACCGTATATCTGGAGCAGCCA
GAAGCCATCGATTACAAACGTTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP25524
UniProtKB Entry NameCODA_ECOLI
GenBank Protein ID581051
GenBank Gene IDX63656
General References
  1. Danielsen S, Kilstrup M, Barilla K, Jochimsen B, Neuhard J: Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase. Mol Microbiol. 1992 May;6(10):1335-44. [Article]
  2. Austin EA, Huber BE: A first step in the development of gene therapy for colorectal carcinoma: cloning, sequencing, and expression of Escherichia coli cytosine deaminase. Mol Pharmacol. 1993 Mar;43(3):380-7. [Article]
  3. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  4. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  5. Porter DJ, Austin EA: Cytosine deaminase. The roles of divalent metal ions in catalysis. J Biol Chem. 1993 Nov 15;268(32):24005-11. [Article]
  6. Ireton GC, Black ME, Stoddard BL: Crystallization and preliminary X-ray analysis of bacterial cytosine deaminase. Acta Crystallogr D Biol Crystallogr. 2001 Nov;57(Pt 11):1643-5. Epub 2001 Oct 25. [Article]
  7. Zhang J, Kale V, Chen M: Gene-directed enzyme prodrug therapy. AAPS J. 2015 Jan;17(1):102-10. doi: 10.1208/s12248-014-9675-7. Epub 2014 Oct 23. [Article]
  8. Ireton GC, McDermott G, Black ME, Stoddard BL: The structure of Escherichia coli cytosine deaminase. J Mol Biol. 2002 Jan 25;315(4):687-97. [Article]
  9. Mahan SD, Ireton GC, Knoeber C, Stoddard BL, Black ME: Random mutagenesis and selection of Escherichia coli cytosine deaminase for cancer gene therapy. Protein Eng Des Sel. 2004 Aug;17(8):625-33. Epub 2004 Sep 20. [Article]
  10. Fuchita M, Ardiani A, Zhao L, Serve K, Stoddard BL, Black ME: Bacterial cytosine deaminase mutants created by molecular engineering show improved 5-fluorocytosine-mediated cell killing in vitro and in vivo. Cancer Res. 2009 Jun 1;69(11):4791-9. doi: 10.1158/0008-5472.CAN-09-0615. [Article]
  11. Hall RS, Fedorov AA, Xu C, Fedorov EV, Almo SC, Raushel FM: Three-dimensional structure and catalytic mechanism of cytosine deaminase. Biochemistry. 2011 Jun 7;50(22):5077-85. doi: 10.1021/bi200483k. Epub 2011 May 12. [Article]
  12. Hitchcock DS, Fedorov AA, Fedorov EV, Dangott LJ, Almo SC, Raushel FM: Rescue of the orphan enzyme isoguanine deaminase. Biochemistry. 2011 Jun 28;50(25):5555-7. doi: 10.1021/bi200680y. Epub 2011 Jun 7. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03939(4S)-4-hydroxy-3,4-dihydro-2(1H)-pyrimidinoneexperimentalunknownDetails
DB04135(4S)-5-Fluoro-4-hydroxy-3,4-dihydro-2(1H)-pyrimidinoneexperimentalunknownDetails