Information on EC 3.5.4.1 - cytosine deaminase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
3.5.4.1
-
RECOMMENDED NAME
GeneOntology No.
cytosine deaminase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytosine + H2O = uracil + NH3
show the reaction diagram
-
-
-
-
cytosine + H2O = uracil + NH3
show the reaction diagram
active site architecture and substrate binding, catalytic mechanism
-
cytosine + H2O = uracil + NH3
show the reaction diagram
substrate binding involves a significant conformational change that sequesters the reaction complex from solvent, active site architecture and substrate binding, catalytic mechanism
-
cytosine + H2O = uracil + NH3
show the reaction diagram
E64 side-chain carboxyl group acts as proton shuttle between the Zn-bound water molecule and cytosine. In course of reaction, cytosine reorients to favor nucleophilic attack by a Zn-bound hydroxide. F114 may be important for reactant binding and product release
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arginine and proline metabolism
-
-
Metabolic pathways
-
-
Pyrimidine metabolism
-
-
pyrimidine metabolism
-
-
pyrimidine nucleobases salvage II
-
-
pyrimidine ribonucleosides salvage III
-
-
SYSTEMATIC NAME
IUBMB Comments
cytosine aminohydrolase
Also acts on 5-methylcytosine.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A3DE
-
-
APOBEC1
P51908
-
APOBEC3
Q99J72
-
APOBEC3
-
-
APOBEC3G
-
-
CD
P25524
-
CDase
Q6Q8Q1
-
CodA protein
P25524
-
CodA protein
Escherichia coli K12
P25524
-
-
Cytosine aminohydrolase
-
-
-
-
cytosine deaminase
-
-
cytosine deaminase
-
-
cytosine deaminase I
-
-
-
cytosine deaminase II
-
-
-
cytosine deaminase S
-
-
cytosine deaminase S
Serratia marcescens type S
-
-
-
cytosine deaminase Y
-
-
Fca1p
Candida dubliniensis isolates SA113, SA109, Eg202, Eg204 and p7276
-
-
-
isocytosine deaminase
-
-
-
-
Zn2+CDase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9025-05-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ssp. denitrificans J9
-
-
Manually annotated by BRENDA team
Achromobacter liquidum
IFO 3084
-
-
Manually annotated by BRENDA team
Achromobacter polymorph
AKU 0122
-
-
Manually annotated by BRENDA team
Achromobacter polymorph AKU 0122
AKU 0122
-
-
Manually annotated by BRENDA team
AKU 0300; IAM 1526
-
-
Manually annotated by BRENDA team
Agrobacterium tumefaciens AKU 0300
AKU 0300
-
-
Manually annotated by BRENDA team
Agrobacterium tumefaciens IAM 1526
IAM 1526
-
-
Manually annotated by BRENDA team
AKU 0101; type S
-
-
Manually annotated by BRENDA team
Alcaligenes faecalis AKU 0101
AKU 0101
-
-
Manually annotated by BRENDA team
Alcaligenes faecalis IAM 0101
IAM 0101
-
-
Manually annotated by BRENDA team
Alcaligenes faecalis type S
type S
-
-
Manually annotated by BRENDA team
Alcaligenes viscolactis
IAM 1517
-
-
Manually annotated by BRENDA team
Alcaligenes viscolactis IAM 1517
IAM 1517
-
-
Manually annotated by BRENDA team
Arthrobacter sp. JH-13
JH-13
-
-
Manually annotated by BRENDA team
Aspergillus fumigatus IFO5840
IFO5840
-
-
Manually annotated by BRENDA team
IFO 3329
-
-
Manually annotated by BRENDA team
ATCC 17759
-
-
Manually annotated by BRENDA team
Candida dubliniensis isolates SA113, SA109, Eg202, Eg204 and p7276
-
-
-
Manually annotated by BRENDA team
strain YK 391, intracellular isoform
-
-
Manually annotated by BRENDA team
Chromobacterium violaceum YK 391
strain YK 391, intracellular isoform
-
-
Manually annotated by BRENDA team
Chromobacterium violaceum YK 391
YK 391
-
-
Manually annotated by BRENDA team
K-1 AKU 0011; S-96 AKU 0009
-
-
Manually annotated by BRENDA team
S-96 AKU 0009
-
-
Manually annotated by BRENDA team
IFO 3319; type S
-
-
Manually annotated by BRENDA team
Enterobacter aerogenes type S
type S
-
-
Manually annotated by BRENDA team
IAM 1221; type S
-
-
Manually annotated by BRENDA team
Enterobacter cloacae IAM 1221
IAM 1221
-
-
Manually annotated by BRENDA team
Enterobacter cloacae type S
type S
-
-
Manually annotated by BRENDA team
enyzme is encoded in codBA operon
-
-
Manually annotated by BRENDA team
gene codA
-
-
Manually annotated by BRENDA team
K-12 IFO 3301
-
-
Manually annotated by BRENDA team
strain K12
SwissProt
Manually annotated by BRENDA team
strain K12 AKU 0005
-
-
Manually annotated by BRENDA team
Escherichia coli GIA39(DE3)
-
SwissProt
Manually annotated by BRENDA team
Escherichia coli K12
strain K12
SwissProt
Manually annotated by BRENDA team
Escherichia coli K12 AKU 0005
strain K12 AKU 0005
-
-
Manually annotated by BRENDA team
Flavobacterium filamentosum
-
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
AKU 0502
-
-
Manually annotated by BRENDA team
Micrococcus flavus AKU 0502
AKU 0502
-
-
Manually annotated by BRENDA team
renal cell carcinoma tumor-bearing mice
-
-
Manually annotated by BRENDA team
IFO 3849; type S
-
-
Manually annotated by BRENDA team
Proteus mirabilis type S
type S
-
-
Manually annotated by BRENDA team
IFO 3167
-
-
Manually annotated by BRENDA team
IFO 3851; type S
-
-
Manually annotated by BRENDA team
Proteus vulgaris type S
type S
-
-
Manually annotated by BRENDA team
IFO 3456; type S
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa type S
type S
-
-
Manually annotated by BRENDA team
IFO 3904; type S
-
-
Manually annotated by BRENDA team
Pseudomonas chlororaphis type S
type S
-
-
Manually annotated by BRENDA team
IFO 12047; type S
-
-
Manually annotated by BRENDA team
Pseudomonas cruciviae type S
type S
-
-
Manually annotated by BRENDA team
IFO 3081; type P
-
-
Manually annotated by BRENDA team
IFO 3458
-
-
Manually annotated by BRENDA team
77 AKU 875; IFO 3738
-
-
Manually annotated by BRENDA team
AKU 0820; ATCC 4359; IFO 3757
-
-
Manually annotated by BRENDA team
IFO 3738; IFO 3757; type S
-
-
Manually annotated by BRENDA team
Pseudomonas putida AKU 0820
AKU 0820
-
-
Manually annotated by BRENDA team
Pseudomonas putida type S
type S
-
-
Manually annotated by BRENDA team
Pseudomonas schuylkilliensis
IFO 12055
-
-
Manually annotated by BRENDA team
Pseudomonas schuylkilliensis
IFO 12055; type S
-
-
Manually annotated by BRENDA team
Pseudomonas schuylkilliensis type S
type S
-
-
Manually annotated by BRENDA team
Pseudomonas trifolii
IFO 12056
-
-
Manually annotated by BRENDA team
Pseudomonas trifolii
IFO 12056; type S
-
-
Manually annotated by BRENDA team
Pseudomonas trifolii type S
type S
-
-
Manually annotated by BRENDA team
IFO 12510; type S
-
-
Manually annotated by BRENDA team
Ralstonia solanacearum type S
type S
-
-
Manually annotated by BRENDA team
baker's yeast; type Y
-
-
Manually annotated by BRENDA team
gene FCY1
SwissProt
Manually annotated by BRENDA team
recombinant protein
SwissProt
Manually annotated by BRENDA team
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
HD11-AE2
-
-
Manually annotated by BRENDA team
IFO 3054; type S
-
-
Manually annotated by BRENDA team
Serratia marcescens type S
type S
-
-
Manually annotated by BRENDA team
Serratia polymuthicum
AKU 0062
-
-
Manually annotated by BRENDA team
Serratia polymuthicum AKU 0062
AKU 0062
-
-
Manually annotated by BRENDA team
pigs express four different A3 mRNAs encoding poA3Z2, poA3Z3, and by read-through transcription and alternatively splicing poA3Z2-Z3 and poA3Z2-Z3 splice variant A (SVA)
-
-
Manually annotated by BRENDA team
Xanthomonas arboricola pv. pruni IAM 1313
IAM 1313
-
-
Manually annotated by BRENDA team
Xanthomonas campestris IAM 1671
IAM 1671
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
human mitochondrial and nuclear DNA are edited by APOBEC3A. The degree of editing is much greater in patients lacking the uracil DNA-glycolyase gene
physiological function
P51908, Q99J72
for woodchuck hepatitis virus mAPOBEC3 is operative
physiological function
P51908, Q99J72
mHBV (mouse transgenic model of HBV replication) is edited in vivo by mAPOBEC1 (mA1) and not mAPOBEC3
physiological function
-
porcine A3 is tested toward their antiretroviral activity against porcine endogenous retrovirus (PERV) and murine leukemia virus (MuLV) using novel single-round reporter viruses. The porcine A3Z2, A3Z3 and A3Z2-Z3 mRNAs are packaged into PERV particles and inhibit PERV replication in a dose-dependent manner. The antiretroviral effect correlate with editing by the porcine A3s with a trinucleotide preference for 5' TGC for A3Z2 and A3Z2-Z3 and 5' CAC for A3Z3
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-thiocytosine + H2O
2-thiouracil + NH3
show the reaction diagram
-
-
-
-
?
3-oxouracil + H2O
?
show the reaction diagram
-
-
-
-
?
5-azacytosine + H2O
5-azauracil + NH3
show the reaction diagram
-
-
-
-
?
5-bromocytosine + H2O
5-bromouracil + NH3
show the reaction diagram
-
-
-
-
?
5-chlorocytosine + H2O
5-chlorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Q12178
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Q6Q8Q1
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
low activity
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
P25524
low activity
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug 5-fluorocytosine to the anticander drug 5-fluorouracil
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
release of 5-fluorouracil is rate-limiting and may involve multiple steps
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug by the recombinant fusion enzyme, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme encoded in an adenoviral vector expressed in murine cancers or human cancer cell lines for prodrug cancer gene therapy, Ad/5HREp-BCD-mediated cytotoxicity under hypoxic conditions, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme in gene therapy in human glioblastoma cell lines Y87-1 and Y87-2
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme in transfected cells, cytotoxic effects of the enzyme expressed form the AdLPCD vector, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme, combination of cytosine deaminase with uracil phosphoribosyl transferase leads to local and distant bystander effects against RM1 prostate cancer in mice in gene-directed enzyme prodrug therapy, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant fusion enzyme, cytotoxicity could be enhanced by concurrently treating TKglyCD-expressing cells with prodrugs ganclocivir and 5-fluorocytosine, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug to the cytotoxic drug in cancer therapy by recombinant adenoviral vector expressed enzyme in human glioma cells, leads to increased 5-fluorouracil-mediated cell killing, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug to the cytotoxic drug in cancer therapy by recombinant enzyme in melanoma cells, leads to increased 5-fluorouracil-mediated cell killing, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug to the cytotoxic drug in cancer therapy by recombinant enzyme, the cytosine deaminase gene acts as suicide gene leading to increased 5-fluorouracil-mediated murine colorectal cancer cell killing, liposomal formulation of substrate 5-fluorocytosine using dipalmitoylphopshatidylcholine and cholesterol in a 1:1 ratio, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug to the cytotoxic drug in cancer therapy through the recombinant fusion enzyme cytosine deaminase/uracil phosphoribosyltransferase in human cancer cell lines, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Q12178
activation of the prodrug to the cytotoxic drug in cancer therapy, gene therapy with the FCY1 gene, encoding the enzyme, alone is not effective in treatement of pancreatic cancer, co-expression with uracil phosphoribosyltranferase encoding gene FUR1, as fusion enzyme, can confer sensitivity to 5-fluorouracil to some pancreatic cancer cells, but not to all, thus it might also not be an effective therapy in pancreatic cancer, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug, 5-fluorouracil is an inhibitor of DNA synthesis and RNA function
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug, product release is the rate-limiting step during the activation to the anticancer drug 5-fluorouracil
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug, the cytosine deaminase gene is an alternative gene for negative selection producing the toxic metabolite 5-fluorouracil, sensitivity of cells to 5-FU can be further increased by expression of uracil phosphoribosyltransferase, which catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
direct inoculation of murine and human brain tumor cell lines, murine neuroblastoma and human glioma cells, with the enzyme transmitted in a recombinant HSV-1 viral oncolytic vector results in cytotoxicity and destruction of cancer cells wth increased cytotoxicity for neighbouring cells, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
reaction of cytosine deaminase, the uracil phosphoribosyl transferase part in a chimeric bifunctional enzyme converts 5-fluorouracil into 5-fluoro-UMP, which is a precursor for the cell toxic 5-fluoro-UTP, used for negative selection of transgenic Plasmodium falciparum parasites
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme expressed in Clostridium sp.
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Q12178
recombinant protein of cytosine deaminase used as antigen for biopanning approach, antibody-directed enzyme-prodrug therapy (GDEPT/ADEPT), binding of specific single chain fragment variable (scFv) with cytosine deaminase does not interfere with enzyme activity
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
P25524
used as negative selection marker system, increased 5-fluorocytosine sensitivity in Streptomyces lividans
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
gene-directed enzyme prodrug therapy (GDEPT) with free and liposomal 5-fluorocytosine (5-FC), antitumor effects of liposomal 5-fluorocytosine (5-FC) increased if compared to free prodrug
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant cytosine deaminase in gene therapy, expression and function in transgenic cell lines and xenograft tumors
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme in gene therapy, expression analysis in transgenic mice with xenograft tumors, optical imaging technologies
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Chromobacterium violaceum YK 391
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Aspergillus fumigatus IFO5840
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Escherichia coli K12
P25524
used as negative selection marker system, increased 5-fluorocytosine sensitivity in Streptomyces lividans
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Candida dubliniensis isolates SA113, SA109, Eg202, Eg204 and p7276
-
-
-
-
?
5-iodocytosine + H2O
5-iodouracil + NH3
show the reaction diagram
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
-
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
Q12178
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
Chromobacterium violaceum YK 391
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
Aspergillus fumigatus IFO5840
-
-
-
-
?
6-azacytosine + H2O
6-azauracil + NH3
show the reaction diagram
-
-
-
-
?
6-azacytosine + H2O
6-azauracil + NH3
show the reaction diagram
Chromobacterium violaceum, Chromobacterium violaceum YK 391
-
-
-
-
?
creatinine + H2O
N-methylhydantoin + NH3
show the reaction diagram
-
-
-
-
?
creatinine + H2O
N-methylhydantoin + NH3
show the reaction diagram
Flavobacterium filamentosum
-
-
-
-
-
creatinine + H2O
N-methylhydantoin + NH3
show the reaction diagram
Escherichia coli K12 AKU 0005
-
-
-
-
?
cytidine + H2O
1-beta-D-ribofuranosylpyrimidin-2(1H)-one + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
P25524
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Q12178
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas schuylkilliensis
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas trifolii
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Achromobacter liquidum, Pseudomonas cruciviae
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia polymuthicum
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas oleovorans, Xanthomonas arboricola pv. pruni, Alcaligenes viscolactis, Achromobacter polymorph
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Flavobacterium filamentosum
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
P25524
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
uracil binding structure at the active site, analysis by ab initio ONIOM-MD simulations showing that uracil is strongly perturbed by Ile33, which sandwiches uracil with His62, through the steric contact due to the thermal motion, detailed overview
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
best substrate
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
the enzyme is a pyrimidine salvage pathway enzyme, inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
treatment of BDIX rat colon cancer cells using the cytosine deaminase/5-fluorocytosine suicide system induces apoptosis, modulation of the proteome, and Hsp90beta phosphorylation, mechanism of the anticancer effect, overview
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
molecular dynamics study of the ligand release path in yeast cytosine deaminase, the active site is well protected by the C-terminal helix, residues 150158, and F-114 loop, residues 111117, substrate binding structure, overview
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
the cytosine deamination proceeds via a sequential mechanism involving the protonation of the N3 of cytosine, a nucleophilic attack on C4 by the Zn-coordinated hydroxide, and the cleavage of the C4-N4 bond, combined two-layer ONIOM quantum chemical-molecular dynamics study, method, development, overview
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Xanthomonas campestris IAM 1671
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter aerogenes type S, Alcaligenes faecalis type S, Serratia marcescens type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia marcescens type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter cloacae IAM 1221
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Xanthomonas arboricola pv. pruni IAM 1313
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes faecalis IAM 0101
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas schuylkilliensis type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Escherichia coli K12 AKU 0005
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas chlororaphis type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Agrobacterium tumefaciens IAM 1526
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Arthrobacter sp. JH-13
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas aeruginosa type S, Pseudomonas putida type S, Proteus mirabilis type S, Pseudomonas trifolii type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Agrobacterium tumefaciens AKU 0300
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter cloacae type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes faecalis AKU 0101
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Chromobacterium violaceum YK 391
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Aspergillus fumigatus IFO5840
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia polymuthicum AKU 0062
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Proteus vulgaris type S, Pseudomonas cruciviae type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Escherichia coli K12
P25524
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes viscolactis IAM 1517, Pseudomonas putida AKU 0820
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Micrococcus flavus AKU 0502
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Achromobacter polymorph AKU 0122
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Ralstonia solanacearum type S
-
-
-
-
?
pyrimidin-2-one + H2O
(4R)-hydroxyl-3,4-dihydropyrimidine + ?
show the reaction diagram
-
stabilization of a transition-state analogue at the active site of cytosine deaminase with importance of proton transfer from the Zn hydroxide group to Glu64 during the nucleophilic attack, quantum mechanical/molecular mechanical molecular dynamics and free energy simulations, active site structure, overview
-
-
?
isocytosine + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
creatinine is no substrate
-
-
-
additional information
?
-
-
5-methylcytosine, cytidine, deoxycytidine and CMP are no substrates
-
-
-
additional information
?
-
-
5-methylcytosine, cytidine, 5'-CMP, adenine, adenosine, 5'-AMP, guanine, guanosine, 5'-GMP and GMP are no substrates
-
-
-
additional information
?
-
P25524
enzyme is an important member of the pyrimidine salvage pathway
-
-
-
additional information
?
-
-
creatinine is a poor substrate for Zn2+CDase and apoCDase
-
-
-
additional information
?
-
-
no substrate: 5-azacytosine
-
-
-
additional information
?
-
-
adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts of murine tumors, e.g. in human cervical epithelial adenocarcinoma cell line HeLa and human pancreatic carcinoma cell line MIA PaCa-2, as well as in human colon carcinoma cell lines WiDr and HT29, overview
-
-
-
additional information
?
-
-
combination of cytosine deaminase suicide gene expression with treatment with antibody against human death receptor DR5 increases cancer cell cytotoxicity, the death receptors are involved in TNF-related factor-induced apoptosis, overview
-
-
-
additional information
?
-
-
cytosine deaminase gene therapy combined with radiation treatment in breast cancer is evaluated in a 4T1murine breast carcinoma model, overview
-
-
-
additional information
?
-
-
cytosine deaminase/5-fluorocytosine exposure induces bystander and radiosensitization effects in hypoxic glioblastoma cell lines Y87-1 and Y87-2 in vitro, overview
-
-
-
additional information
?
-
-
low-dose etoposide enhances telomerase-dependent adenovirus-mediated cytosine deaminase gene therapy through augmentation of adenoviral infection and transgene expression in a syngeneic bladder tumor model, overview
-
-
-
additional information
?
-
-
the cytosine deaminase gene acts as a suicide gene by catalyzing the conversion of 5-fluorocytosine to cytotoxic 5-fluorouracil, fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit in cancer gene therapy of gliosarcoma cells and murine 9L tumors, overview
-
-
-
additional information
?
-
-
the enzyme is useful in gene therapy of cancers, conjugation of poly-L-lysine to cytosine deaminase improves the efficacy of enzyme/prodrug cancer therapy, e.g. by a 50times higher cellular uptake than that of control molecules in human breast MDA-MB-231 cancer cells and increase stability after uptake into cells, uptake and intracellular distribution, mechanisms, overview
-
-
-
additional information
?
-
-
the enzyme is useful in treatment of human ovarian cancer by genetic prodrug activation therapy with procaspase-3 co-expression improving the method, overview
-
-
-
additional information
?
-
-
a small fraction of human mitochondrial genomes are edited by APOBEC3 deaminases in the cytoplasm. Nuclear DNA tably segments of MYC and TP53, can be hyperedited by APOBEC3A
-
-
-
additional information
?
-
Serratia marcescens type S
-
5-methylcytosine, cytidine, 5'-CMP, adenine, adenosine, 5'-AMP, guanine, guanosine, 5'-GMP and GMP are no substrates
-
-
-
additional information
?
-
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
-
5-methylcytosine, cytidine, deoxycytidine and CMP are no substrates
-
-
-
additional information
?
-
Pseudomonas putida type S
-
-
-
-
-
additional information
?
-
Chromobacterium violaceum YK 391
-
no substrate: 5-azacytosine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug 5-fluorocytosine to the anticander drug 5-fluorouracil
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
activation of the prodrug by the recombinant fusion enzyme, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme encoded in an adenoviral vector expressed in murine cancers or human cancer cell lines for prodrug cancer gene therapy, Ad/5HREp-BCD-mediated cytotoxicity under hypoxic conditions, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme in gene therapy in human glioblastoma cell lines Y87-1 and Y87-2
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme in transfected cells, cytotoxic effects of the enzyme expressed form the AdLPCD vector, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant enzyme, combination of cytosine deaminase with uracil phosphoribosyl transferase leads to local and distant bystander effects against RM1 prostate cancer in mice in gene-directed enzyme prodrug therapy, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
-
recombinant fusion enzyme, cytotoxicity could be enhanced by concurrently treating TKglyCD-expressing cells with prodrugs ganclocivir and 5-fluorocytosine, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Q12178
recombinant protein of cytosine deaminase used as antigen for biopanning approach, antibody-directed enzyme-prodrug therapy (GDEPT/ADEPT), binding of specific single chain fragment variable (scFv) with cytosine deaminase does not interfere with enzyme activity
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
show the reaction diagram
Escherichia coli, Escherichia coli K12
P25524
used as negative selection marker system, increased 5-fluorocytosine sensitivity in Streptomyces lividans
-
-
?
5-methylcytosine + H2O
thymine + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas schuylkilliensis
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas trifolii
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Achromobacter liquidum, Pseudomonas cruciviae
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia polymuthicum
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas oleovorans, Xanthomonas arboricola pv. pruni, Alcaligenes viscolactis, Achromobacter polymorph
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Flavobacterium filamentosum
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
P25524
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
the enzyme is a pyrimidine salvage pathway enzyme, inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
treatment of BDIX rat colon cancer cells using the cytosine deaminase/5-fluorocytosine suicide system induces apoptosis, modulation of the proteome, and Hsp90beta phosphorylation, mechanism of the anticancer effect, overview
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Xanthomonas campestris IAM 1671
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter aerogenes type S, Alcaligenes faecalis type S, Serratia marcescens type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia marcescens type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter cloacae IAM 1221
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Xanthomonas arboricola pv. pruni IAM 1313
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes faecalis IAM 0101
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas schuylkilliensis type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Escherichia coli K12 AKU 0005
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas chlororaphis type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Agrobacterium tumefaciens IAM 1526
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Arthrobacter sp. JH-13
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Pseudomonas aeruginosa type S, Pseudomonas putida type S, Proteus mirabilis type S, Pseudomonas trifolii type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Agrobacterium tumefaciens AKU 0300
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Enterobacter cloacae type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes faecalis AKU 0101
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Chromobacterium violaceum YK 391
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Aspergillus fumigatus IFO5840
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Serratia polymuthicum AKU 0062
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Proteus vulgaris type S, Pseudomonas cruciviae type S
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Escherichia coli K12
P25524
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Alcaligenes viscolactis IAM 1517, Pseudomonas putida AKU 0820
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Micrococcus flavus AKU 0502
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Achromobacter polymorph AKU 0122
-
-
-
-
?
cytosine + H2O
uracil + NH3
show the reaction diagram
Ralstonia solanacearum type S
-
-
-
-
?
additional information
?
-
P25524
enzyme is an important member of the pyrimidine salvage pathway
-
-
-
additional information
?
-
-
adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts of murine tumors, e.g. in human cervical epithelial adenocarcinoma cell line HeLa and human pancreatic carcinoma cell line MIA PaCa-2, as well as in human colon carcinoma cell lines WiDr and HT29, overview
-
-
-
additional information
?
-
-
combination of cytosine deaminase suicide gene expression with treatment with antibody against human death receptor DR5 increases cancer cell cytotoxicity, the death receptors are involved in TNF-related factor-induced apoptosis, overview
-
-
-
additional information
?
-
-
cytosine deaminase gene therapy combined with radiation treatment in breast cancer is evaluated in a 4T1murine breast carcinoma model, overview
-
-
-
additional information
?
-
-
cytosine deaminase/5-fluorocytosine exposure induces bystander and radiosensitization effects in hypoxic glioblastoma cell lines Y87-1 and Y87-2 in vitro, overview
-
-
-
additional information
?
-
-
low-dose etoposide enhances telomerase-dependent adenovirus-mediated cytosine deaminase gene therapy through augmentation of adenoviral infection and transgene expression in a syngeneic bladder tumor model, overview
-
-
-
additional information
?
-
-
the cytosine deaminase gene acts as a suicide gene by catalyzing the conversion of 5-fluorocytosine to cytotoxic 5-fluorouracil, fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit in cancer gene therapy of gliosarcoma cells and murine 9L tumors, overview
-
-
-
additional information
?
-
-
the enzyme is useful in gene therapy of cancers, conjugation of poly-L-lysine to cytosine deaminase improves the efficacy of enzyme/prodrug cancer therapy, e.g. by a 50times higher cellular uptake than that of control molecules in human breast MDA-MB-231 cancer cells and increase stability after uptake into cells, uptake and intracellular distribution, mechanisms, overview
-
-
-
additional information
?
-
-
the enzyme is useful in treatment of human ovarian cancer by genetic prodrug activation therapy with procaspase-3 co-expression improving the method, overview
-
-
-
additional information
?
-
-
a small fraction of human mitochondrial genomes are edited by APOBEC3 deaminases in the cytoplasm. Nuclear DNA tably segments of MYC and TP53, can be hyperedited by APOBEC3A
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
BaCl2
-
1.0 mM, relative activity 110%
BaCl2
-
1.0 mM, relative activity 105%
CaCl2
-
1.0 mM, relative activity 113%
CaCl2
-
1 mM, relative activity 111%
Co2+
-
Mn2+ reconstitutes apoenzyme after removal of Fe2+
Fe2+
-
catalytically essential divalent metal ion
Fe2+
-
bound to the enzyme, very rapid complex formation
Fe2+
-
bound to the active site, the metal ion coordinates a hydroxyl nucleophile, binding structure, overview
FeCl3
-
1.0 mM, relative activity 115%
FeCl3
-
1.0 mM, relative activity 130%
Iron
-
the enzyme contains 0.20 equivalents of Fe
KCl
-
1.0 mM, relative activity 116%
MnCl2
-
1 mM, relative activity 113%
MnCl2
-
Mn2+ reconstitutes apoenzyme after removal of Fe2+
NaCl
-
1.0 mM, relative activity 107%
SnCl2
-
1.0 mM, relative activity 122%
Zinc
-
the enzyme contained 0.56 equivalents of Zn
Zn2+
-
Mn2+ reconstitutes apoenzyme after removal of Fe2+
Zn2+
-
bound to the enzyme, below 0.2 mol per mol of subunit, reconstitution of apoenzyme
Zn2+
-
1 metal ion is tightly bound to the active site, binding structure modeling, Fourier mapping
Zn2+
-
enzyme bound, binding structure, overview
Zn2+
-
ligands are two cysteines, a histidine, and one water molecule
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2S)-(-)-ephedrine
-
-
(alpha-D-glucopyranosylthio)gold
-
-
(R)-2,10,11-trihydroxy-N-propyl-noraporphine
-
-
-
(R)-2,10,11-trihydroxyaporphine
-
-
(R)-apomorphine
-
-
(R)-N-allylnorapomorphine
-
-
(R)-propylnorapomorphine
-
-
(S)-carbidopa
-
-
1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
-
-
2,2'-dipyridyl
-
-
2-hydroxypyrimidine
-
-
2-hydroxypyrimidine
-
binding structure modeling, inhibition mechanism, acts as a transition state analogue
2-pyrimidinone
-
-
2-thiocytosine
-
weak
2-Thiouracil
-
strong
3,4-dihydroxyphenylacetic acid
-
-
4-chloromercuribenzoic acid
-
-
4-[(2-sulfanyl-1H-imidazol-1-yl)methyl]phenol
-
-
5'-guanidinonaltrindole
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
-
-
5-Azacytosine
-
weak
5-bromo-2-pyrimidinone
-
-
5-fluoro-1H-pyrimidin-2-one
-
19F NMR experiments show that binding of the inhibitor 5-fluoro-1H-pyrimidin-2-one (5FPy) to the wild-type yCD causes an upfield shift, indicating that the bound inhibitor is in the hydrated form, mimicking the transition state or the tetrahedral intermediate in the activation of 5FC. Binding of 5FPy to the E64A mutant enzyme causes a downfield shift, indicating that the bound 5FPy remains in an unhydrated form in the complex with the mutant enzyme
-
5-fluoro-4-(S)-hydroxyl-3,4-dihydropyrimidine
-
mechanism-based inhibitor
6-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene
-
-
-
6-hydroxy-DL-DOPA
-
-
alpha,alpha'-dipyridyl
-
-
aurintricarboxylic acid
-
-
caffeic acid
-
-
cephapirin
-
-
chloramine-T
-
complete inhibition, reversed by cytosine
Cu2+
-
Fe2+CDase
deoxyguanosine
-
-
dephostatin
-
-
diethyldicarbonate
-
-
dihydrexidine
-
-
ebselen
-
-
ganciclovir
-
-
H2O2
-
only Fe2+CDase, Mn2+CDase, Co2+CDase and Zn2+CDase are not inhibited
Hg(CH3COO)2
-
-
hispidin
-
-
hydroquinone
-
-
Iodine
-
complete inhibition, reversed by cytosine
iodoacetamide
-
-
Mersalyl acid
-
-
methyl 3-hydroxy-DL-tyrosinate
-
-
myricetin
-
-
N-acetyldopamine
-
-
N-bromosuccinimide
-
-
N-bromosuccinimide
-
complete inhibition, reversed by cytosine
N-bromosuccinimide
-
-
nordihydroguaiaretic acid
-
-
o-phenanthroline
-
-
o-phenanthroline
-
removes Fe2+ from the Fe2+CDase to give the apoenzyme, cause of loss in activity, reversible by Fe2+ addition, poor effect on Zn2+CDase
p-benzoquinone
-
-
p-chloromercuribenzoate
-
complete inhibition, reversed by cytosine, cysteine, dithiothreitol or 2-mercaptoethanol
p-chloromercuribenzoate
-
-
p-chloromercuribenzoic acid
-
-
p-chloromercuribenzoic acid
-
-
p-chloromercuribenzoic acid
-
-
p-chloromercuribenzoic acid
-
-
p-Chloromercuriphenylsulfonic acid
-
-
p-hydroxymercuribenzoate
-
-
p-mercuribenzoate
-
0.3 mM, 50% inhibition
phenylmethylsulfonyl fluoride
-
strong, reversed by cytosine
phosphonocytosine
-
-
-
piceatannol
-
-
PPNDS tetrasodium
-
-
pyridoxal 5'-phosphate
-
strong, reversed by cytosine
SCH202676
-
-
SKF-89626
-
-
Zn2+
-
Fe2+CDase
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
-
1.0 mM + glycine methyl ester, relative activity 102%
2-mercaptoethanol
-
1 mM, relative activity 108%
alpha,alpha'-dipyridyl
-
1 mM, relative activity 104%
ATP
-
10.0 mM, relative activity 154%
ATP
-
1.0 mM, substrate cytosine, relative activity 105%, substrate 5-methylcytosine relative activity 113%
D-alanine
-
1 mM, relative activity 120%
D-threonine
-
1 mM, relative activity 120%
dAMP
-
10.0 mM, relative activity 154%
dGMP
-
1.0 mM, substrate cytosine, relative activity 109%
diethyldicarbonate
-
1.0 mM, relative activity 102%
DL-alpha-amino-n-butyric acid
-
1 mM, relative activity 140%
DL-homoserine
-
1 mM, relative activity 110%
DL-isoleucine
-
1 mM, relative activity 130%
DL-methionine
-
1mM, relative activity 140%
EDTA
-
1 mM, relative activity 111%
EDTA
-
1 mM, relative activity 101%
ethylacetoimidate
-
1.0 mM, relative activity 101%
ethylacetoimidate
-
-
ethylacetoimidate
-
-
ethylacetoimidate
-
1.0 mM, relative activity 102%
GDP
-
10.0 mM, relative activity 176%
glycine
-
1 mM, relative activity 130%
GTP
-
10.0 mM, relative activity 171%
IDP
-
10.0 mM, relative activity 152%
ITP
-
10.0 mM, relative activity 155%
L-amino acids
-
-
L-asparagine
-
10.0 mM, relative activity 150%
L-asparagine
-
10.0 mM, relative activity 156%
L-asparagine
-
-
L-aspartic acid
-
-
L-aspartic acid
-
10.0 mM, relative activity 144%
L-aspartic acid
-
10.0 mM, relative activity 158%
L-aspartic acid
-
1 mM, relative activity 130%
L-aspartic acid
-
-
L-cysteine
-
10.0 mM, relative activity 160%
L-cysteine
-
10.0 mM, relative activity 138%
L-Glutamic acid
-
-
L-Glutamic acid
-
10.0 mM, relative activity 138%
L-Glutamic acid
-
10.0 mM, relative activity 135%
L-Glutamic acid
-
1 mM, relative activity 120%
L-Glutamic acid
-
-
L-glutamine
-
-
L-glutamine
-
10.0 mM, relative activity 143%
L-glutamine
-
10.0 mM, relative activity 120%
L-glutamine
-
1 mM, relative activity 130%
L-glutamine
-
-
L-histidine
-
-
L-histidine
-
10.0 mM, relative activity 160%
L-histidine
-
10.0 mM, relative activity 148%
L-histidine
-
1 mM, relative activity 120%
L-hydroxyproline
-
-
L-hydroxyproline
-
10.0 mM, relative activity 150%
L-hydroxyproline
-
10.0 mM, relative activity 141%
L-hydroxyproline
-
1 mM, relative activity 120%
L-hydroxyproline
-
-
L-isoleucine
-
1 mM, relative activity 130%
L-leucine
-
1 mM, relative activity 120%
L-methionine
-
10.0 mM, relative activity 150%
L-methionine
-
10.0 mM, relative activity 139%
L-methionine
-
-
L-ornithine
-
1 mM, relative activity 120%
L-phenylalanine
-
1 mM, relative activity 140%
L-serine
-
1 mM, relative activity 140%
L-threonine
-
1 mM, relative activity 120%
NaCN
-
1 mM, relative activity 104%
phosphate
-
1.0 mM, relative activity 170%
phosphate
-
1.0 mM, relative activity 140%
Sodium azide
-
1 mM, relative activity 101%
sulfate
-
1.0 mM, relative activity 110%
sulfite
-
1.0 mM, relative activity 105%
trichloroacetate
-
1 mM, relative activity 101%
L-valine
-
1 mM, relative activity 120%
additional information
-
low-dose etoposide enhances telomerase-dependent adenovirus-mediated cytosine deaminase gene therapy through augmentation of adenoviral infection and transgene expression in a syngeneic bladder tumor model, overview
-
additional information
-
during hypoxia in Y87-1 and Y87-2 cells, a hypoxia-responsive element regulates expression of the cytosine deaminase gene and facilitates the conversion of 5-fluorocytosine to 5-fluorouracil
-
additional information
-
conjugation of poly-L-lysine to cytosine deaminase improves the efficacy of enzyme/prodrug cancer therapy, e.g. by a 50times higher cellular uptake than that of control molecules in human breast MDA-MB-231 cancer cells and increase stability after uptake into cells, uptake and intracellular distribution, mechanisms, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
2-thiocytosine
-
pH 7.5, 25C, CDase
0.109
2-thiocytosine
-
pH 7.5, 25C, Zn2+CDase
0.85
3-oxouracil
-
mutant E217A, pH 8.5, 30C
-
4.1
3-oxouracil
-
wild-type, pH 8.5, 30C
-
0.12
5-Azacytosine
-
pH 7.5, 25C, CDase
0.36
5-Azacytosine
-
pH 7.5, 25C, Zn2+CDase
0.117
5-bromocytosine
-
-
0.068
5-fluorocytosine
-
mutant A23L/D92E/V108I/I140L
0.083
5-fluorocytosine
-
wild-type enzyme
0.11
5-fluorocytosine
-
pH 7.5, 25C, transient kinetics
0.14
5-fluorocytosine
-
mutant D92E
0.15
5-fluorocytosine
-
mutant A23L/V108I/I140L
0.16
5-fluorocytosine
-
pH 7.5, 25C, steady-state kinetics
0.16
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
0.26
5-fluorocytosine
-
pH 7.3, 37C
0.33
5-fluorocytosine
-
purified hyaluronan binding domain of TSG-6-cytosine deaminase fusion protein, in PBS buffer, pH not specified in the publication, at 37C
0.51
5-fluorocytosine
-
recombinant cytosine deaminase, in PBS buffer, pH not specified in the publication, at 37C
0.87
5-fluorocytosine
-
pH 7.5, 30C
1.7
5-fluorocytosine
-
pH 7.5, 25C, CDase
2.1
5-fluorocytosine
-
pH 7.5, 37C, mutant F316A
2.8
5-fluorocytosine
-
pH 7.5, 37C, mutant D314A
2.8
5-fluorocytosine
-
mutant D314A, pH 7.5, 37C
3.3
5-fluorocytosine
-
pH 7.5, 37C, wild-type
3.3
5-fluorocytosine
-
wild-type, pH 7.5, 37C
3.76
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
3.9
5-fluorocytosine
-
pH 7.5, 25C, wild-type enzyme
6.5
5-fluorocytosine
-
-
6.6
5-fluorocytosine
-
mutant D314S, pH 7.5, 37C
6.73
5-fluorocytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
7.55
5-fluorocytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
8 - 9
5-fluorocytosine
-
mutant E64A, pH 7.5, temperature not specified in the publication
10.9
5-fluorocytosine
-
mutant D314G, pH 7.5, 37C
11.2
5-fluorocytosine
-
pH 7.5, 25C, Zn2+CDase
12.69
5-fluorocytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
19
5-fluorocytosine
-
mutant E64D, pH 7.5, temperature not specified in the publication
2.32
5-Methylcytosine
-
pH 7.5, 30C
2.5
5-Methylcytosine
-
-
36
5-Methylcytosine
-
-
1.02
6-azacytosine
-
pH 7.5, 25C, Zn2+CDase
1.6
6-azacytosine
-
pH 7.5, 25C, CDase
25
creatinine
-
wild-type, pH 8.5, 30C
0.19
cytosine
-
pH 7.5, 25C, wild-type enzyme
0.2
cytosine
-
pH 7.5, 25C, CDase; pH 7.5, 25C, Zn2+CDase
0.2
cytosine
-
pH 7.5, 37C, mutant F316A; pH 7.5, 37C, wild-type
0.2
cytosine
-
wild-type, pH 7.5, 37C
0.22
cytosine
-
-
0.25
cytosine
-
mutant H246Q, pH 8.5, 30C
0.3
cytosine
-
mutant D314G, pH 7.5, 37C
0.38
cytosine
-
pH 7.5, 30C
0.46
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
0.47
cytosine
-
mutant A23L/D92E/V108I/I140L
0.52
cytosine
-
mutant A23L/V108I/I140L
0.57
cytosine
-
mutant D92E
0.7
cytosine
-
pH 7.5, 37C, mutant H312A
0.8
cytosine
-
pH 7.5, 37C, mutant P318A
0.97
cytosine
-
wild-type, pH 8.5, 30C
1
cytosine
-
at pH 5,7 and 8
1
cytosine
-
mutant D314S, pH 7.5, 37C
1.1
cytosine
-
at pH 6.4
1.1
cytosine
-
pH 7.5, 25C, steady-state kinetics
1.17
cytosine
-
wild-type enzyme
1.25
cytosine
-
-
1.57
cytosine
-
at pH 8.4
1.65
cytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
1.78
cytosine
-
at pH 7.4
1.82
cytosine
-
pH 7.3, 37C
1.9
cytosine
-
mutant D313N, pH 8.5, 30C
2
cytosine
-
-
2.2
cytosine
-
pH 7.5, 37C, mutant D314A
2.2
cytosine
-
mutant D314A, pH 7.5, 37C
3.16
cytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
3.4
cytosine
-
-
4.9
cytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
0.46
isocytosine
-
wild-type, pH 8.5, 30C
additional information
additional information
-
pre-steady-state and steady-state kinetics and thermodynamics of cytosine substrate binding to apoenzyme and Zn2+-holoenzyme
-
additional information
additional information
-
the kinetics of the enzyme associated with poly-L-lysine derivatives are very similar to the wild-type enzyme kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.27
2-thiocytosine
-
pH 7.5, 25C, Zn2+CDase
22.3
2-thiocytosine
-
pH 7.5, 25C, CDase
0.18
3-oxouracil
-
mutant E217A, pH 8.5, 30C
-
2.3
3-oxouracil
-
wild-type, pH 8.5, 30C
-
0.65
5-Azacytosine
-
pH 7.5, 25C, Zn2+CDase
2.68
5-Azacytosine
-
pH 7.5, 25C, CDase
0.00013
5-fluorocytosine
-
mutant E64A, pH 7.5, temperature not specified in the publication
0.005
5-fluorocytosine
-
mutant E64D, pH 7.5, temperature not specified in the publication
5.5
5-fluorocytosine
-
pH 7.5, 25C, Zn2+CDase
9.5
5-fluorocytosine
-
mutant A23L/D92E/V108I/I140L
16
5-fluorocytosine
-
pH 7.5, 25C, CDase
17
5-fluorocytosine
-
pH 7.5, 25C, steady-state kinetics
17
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
18.8
5-fluorocytosine
-
wild-type enzyme
19.71
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
21
5-fluorocytosine
-
pH 7.5, 25C, transient kinetics
29.5
5-fluorocytosine
-
mutant D92E
31.7
5-fluorocytosine
-
mutant A23L/V108I/I140L
71
5-fluorocytosine
-
pH 7.5, 25C, wild-type enzyme
74.3
5-fluorocytosine
-
pH 7.5, 37C, mutant F316A
75.6
5-fluorocytosine
-
pH 7.5, 37C, wild-type
75.6
5-fluorocytosine
-
wild-type, pH 7.5, 37C
83.68
5-fluorocytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
97.7
5-fluorocytosine
-
mutant D314G, pH 7.5, 37C
101.7
5-fluorocytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
115.2
5-fluorocytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
137
5-fluorocytosine
-
mutant D314A, pH 7.5, 37C
137.4
5-fluorocytosine
-
pH 7.5, 37C, mutant D314A
233
5-fluorocytosine
-
mutant D314S, pH 7.5, 37C
5.4
6-azacytosine
-
pH 7.5, 25C, Zn2+CDase
186
6-azacytosine
-
pH 7.5, 25C, CDase
5.6
creatinine
-
wild-type, pH 8.5, 30C
0.0075
cytosine
-
mutant D313N, pH 8.5, 30C
0.18
cytosine
-
mutant H246Q, pH 8.5, 30C
1.69
cytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
2.13
cytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
2.98
cytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
9.5
cytosine
-
mutant A23L/D92E/V108I/I140L
26.4
cytosine
-
pH 7.5, 25C, Zn2+CDase
29.5
cytosine
-
mutant D92E
31.7
cytosine
-
mutant A23L/V108I/I140L
36.8
cytosine
-
mutant D314G, pH 7.5, 37C
49.68
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
91
cytosine
-
pH 7.5, 25C, steady-state kinetics
104
cytosine
-
pH 7.5, 37C, mutant D314A
104
cytosine
-
mutant D314A, pH 7.5, 37C
132
cytosine
-
wild-type, pH 8.5, 30C
165
cytosine
-
pH 7.5, 37C, wild-type
165
cytosine
-
wild-type, pH 7.5, 37C
170
cytosine
-
wild-type enzyme
185
cytosine
-
pH 7.5, 25C, CDase
185
cytosine
-
pH 7.5, 25C, wild-type enzyme
189
cytosine
-
pH 7.5, 37C, mutant H312A
279
cytosine
-
mutant D314S, pH 7.5, 37C
1030
cytosine
-
pH 7.5, 37C, mutant P318A
2286
cytosine
-
pH 7.5, 37C, mutant F316A
5.1
isocytosine
-
wild-type, pH 8.5, 30C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.21
3-oxouracil
-
mutant E217A, pH 8.5, 30C
0
0.56
3-oxouracil
-
wild-type, pH 8.5, 30C
0
0.0000014
5-fluorocytosine
-
mutant E64A, pH 7.5, temperature not specified in the publication
1252
0.00026
5-fluorocytosine
-
mutant E64D, pH 7.5, temperature not specified in the publication
1252
5.24
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
1252
8.02
5-fluorocytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
1252
12.44
5-fluorocytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
1252
15.27
5-fluorocytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
1252
106
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
1252
0.22
creatinine
-
wild-type, pH 8.5, 30C
2015
0.004
cytosine
-
mutant D313N, pH 8.5, 30C
489
0.35
cytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
489
0.72
cytosine
-
mutant H246Q, pH 8.5, 30C
489
0.94
cytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
489
1.29
cytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
489
106.8
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
489
140
cytosine
-
wild-type, pH 8.5, 30C
489
11
isocytosine
-
wild-type, pH 8.5, 30C
6539
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00086
5-fluoro-1H-pyrimidin-2-one
-
wild-type, pH 7.5, temperature not specified in the publication
-
1.06
5-fluoro-1H-pyrimidin-2-one
-
mutant E64D, pH 7.5, temperature not specified in the publication
-
0.3
p-mercuribenzoate
-
-
0.000052
phosphonocytosine
-
pH 8.5, 30C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0013
(1R,2S)-(-)-ephedrine
-
pH 7.4, 37C
0.00036
(alpha-D-glucopyranosylthio)gold
-
pH 7.4, 37C
0.013
(R)-2,10,11-trihydroxy-N-propyl-noraporphine
-
pH 7.4, 37C
-
0.0017
(R)-2,10,11-trihydroxyaporphine
-
pH 7.4, 37C
0.0013
(R)-apomorphine
-
pH 7.4, 37C
0.0029
(R)-N-allylnorapomorphine
-
pH 7.4, 37C
0.006
(R)-propylnorapomorphine
-
pH 7.4, 37C
0.0053
(S)-carbidopa
-
pH 7.4, 37C
0.027
1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
-
pH 7.4, 37C
0.019
3,4-dihydroxyphenylacetic acid
-
pH 7.4, 37C
0.00013
4-chloromercuribenzoic acid
-
pH 7.4, 37C
0.0035
4-[(2-sulfanyl-1H-imidazol-1-yl)methyl]phenol
-
pH 7.4, 37C
0.0064
5'-guanidinonaltrindole
-
pH 7.4, 37C
0.0007
6-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene
-
pH 7.4, 37C
-
0.004
6-hydroxy-DL-DOPA
-
pH 7.4, 37C
0.00049
aurintricarboxylic acid
-
pH 7.4, 37C
0.085
caffeic acid
-
pH 7.4, 37C
0.0075
cephapirin
-
pH 7.4, 37C
0.00043
dephostatin
-
pH 7.4, 37C
0.0091
dephostatin
-
pH 7.4, 37C
0.00059
dihydrexidine
-
pH 7.4, 37C
0.0028
ebselen
-
pH 7.4, 37C
0.6
ganciclovir
-
37C, recombinant fusion protein HSV-1TKglyCD
0.002
hispidin
-
pH 7.4, 37C
0.0026
hydroquinone
-
pH 7.4, 37C
0.003
iodoacetamide
-
pH 7.4, 37C
0.013
methyl 3-hydroxy-DL-tyrosinate
-
pH 7.4, 37C
0.0034
myricetin
-
pH 7.4, 37C
0.00045
N-acetyldopamine
-
pH 7.4, 37C
0.0088
nordihydroguaiaretic acid
-
pH 7.4, 37C
0.00017
p-benzoquinone
-
pH 7.4, 37C
0.0018
piceatannol
-
pH 7.4, 37C
0.0056
PPNDS tetrasodium
-
pH 7.4, 37C
0.029
SCH202676
-
pH 7.4, 37C
0.0013
SKF-89626
-
pH 7.4, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.12
-
(NH4)2SO4 as nitrogen source
0.22
Pseudomonas schuylkilliensis, Pseudomonas trifolii
-
-
0.26
-
strain K-1 AKU 0011
0.32
-
strain AKU 0009
1
-
asparagine as nitrogen source
2
-
+ 0.025 mM Cu(C2H3O2)
2.6
-
+ 0.025 mM HgCl2; + 0.025 mM Pb(C2H3O2)
2.7
-
cytosine as nitrogen source
2.7
-
+ 0.025 mM CrCl2
2.9
-
apoCDase, + 0.025 SnCl2
3.1
-
+ 0.025 mM Cu(C2H3O2)
3.2
-
+ 0.025 mM CaCl2
4
-
+ 0.025 mM NiCl2, additional incubation with 0.025 mM Fe2+
5.6
-
+ 0.025 mM NiCl2
8.3
-
+ 0.025 mM Pb(C2H3O2), additional incubation of 0.025 mM Fe2+
11
-
+ 0.025 mM HgCl2, additional incubation with 0.025 mM Fe2+
12
-
+ 0.025 mM Zn(C2H3O2), additional incubation with 0.025 mM Fe2+
13
-
+ 0.025 mM Zn(C2H3O2)
21
-
+ 0.025 mM CoSO4, additional incubation with 0.025 mM Fe2+
26
-
+ 0.025 mM CoSO4
45
-
+ 0.025 mM MnSO4
58
-
wild-type enzyme, substrate 5-fluorocytosine
62
-
+ 0.025 mM MnSO4, additional incubation with 0.025 mM Fe2+
65
-
+ 0.025 mM FeSO4, additional incubation with 0.025 mM Fe2+
87
-
+ 0.025 mM CrCl2, additional incubation with 0.025 mM Fe2+; + 0.025 mM FeSO4; apoCDase, additional incubation with 0.025 mM Fe2+
88
-
+ 0.025 mM CaCl2, additional incubation with 0.025 mM Fe2+
94
-
+ 0.025 SnCl2, additional incubation with 0.025 mM Fe2+
144
-
wild-type enzyme, substrate cytosine
additional information
-
pH-indicator assay for the measurement of the steady-state kinetic parameters of deamination reaction
additional information
-
development of cell lines and animal xenograft models, expression and function of fusion constructs between cytosine deaminase and monomeric DsRed (mDsRed), analyzed by Western blot, flow cytometry, fluorescence microscopy, magnetic resonance spectroscopy, analysis of antitumoral effect of 5-fluorouracil (5-FU) and 5-fluorocytosine (5-FC) in transgenic background, increase of cytosine deaminase enhances the potential of gene-directed enzyme prodrug therapy, conversion of 5-fluorocytosine to 5-fluorouracil analyzed in mice bearing tumor xenografts with the fusion product between cytosine deaminase and monomeric DsRed (R3327-CD/mDsRed)
additional information
-
incubation of transfected cells increasing concentrations of free or liposomal 5-fluorocytosine (5-FC) for 72 h, effectivness gene-directed enzyme prodrug therapy (GDEPT) tested in mice transplantated with MC-38 tumor cells, survival times of mice bearing tumors, local concentration and toxicity of liposomal prodrug in different organs, enhancement of antitumor effects by liposomal form of 5-fluorocytosine (5-FC)
additional information
P25524
cytosine deaminase of Escherichia coli used as a negative selection marker in Streptomyces, can be applied for any actinobacterial species naturally resistant to 5-fluorocytosine while sensitive to 5-fluorouracil, valuable addition to the actinobacterial genetic toolbox
additional information
-
selection and characterization of a human monoclonal antibody in single chain fragment (scFv) format for detection of expression of cytosine deaminase in GDEPT/ADEPT studies, selection and characterization of specific single chain fragment variable (scFv) antibody specific for cytosine deaminase, cytotoxic assay, amino acid sequence of the CDR3 regions of the selected antibody and genetic structure of phage antibody from ETH-2 library determined, human antibody generated by this method to detect cytosine deaminase in routinary laboratory techniques without interfering with its enzymatic function
additional information
-
capability of human adipose tissue-derived mesenchymal stem cells (AT-MSC) as vehicles for gene-directed enzyme prodrug therapy, fusion product of cytosine deaminase derived from yeast in combination with systemic 5-fluorocytosine (5-Fc), expression and antitumoral effects of fusion constructs tested in cell lines and xenograft models, in vivo analysis in immunodeficient mouse model, regression in 89% of tumors achieved, therapeutic cell homing into subcutaneous melanoma and inhibition of tumor growth
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
P51908, Q99J72
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
a small fraction of human mitochondrial genomes are edited by APOBEC3 deaminases in the cytoplasm
Manually annotated by BRENDA team
Arthrobacter sp. JH-13
-
strain JH-13
-
-
Manually annotated by BRENDA team
Chromobacterium violaceum YK 391, Aspergillus fumigatus IFO5840
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
-
gel filtration
713064
31000
-
gel filtration
209501
32000
-
SDS-PAGE
209501, 209507
34000
-
gel filtration
209484
34000
-
-
209487, 209488, 209492, 209501
35000
-
cytosine deaminase II, gel filtration
209499
37000
-
cytosine deaminase II, gel filtration
209499
37000
-
-
209499, 209501
41000
-
-
209501
90000
-
recombinant fusion protein HSV-1TKglyCD
684863
126000
-
-
669819
156000
-
-
209508
200000
-
gel filtration
209497, 209498
200000
-
-
209498
200000
-
cytosine deaminase I, gel filtration
209499
210000
-
-
209502
260000
-
-
209498
300000
-
gel filtration
209498
580000
-
gel filtration
209487, 209488
580000
-
-
209490, 209501
630000
-
gel filtration
209488
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 18000-20000, cytosine deaminase, SDS-PAGE, x * 45000-50000, recombinant His6-tagged yeast cytosine deaminase/single chain fragment variable human antibody fusion protein, SDS-PAGE
dimer
-
2 * 63000, SDS-PAGE
dimer
-
2 * 78000
dimer
-
recombinant fusion protein HSV-1TKglyCD, SDS-PAGE
dimer
Chromobacterium violaceum YK 391
-
2 * 78000, 2 * 63000, SDS-PAGE
-
hexamer
-
6 * 48000, (alphabeta)8 barrel structure, crystal structure
homodimer
-
2 * 19000, theoretical value
monomer
-
1 * 32000, SDS-PAGE
octamer
-
8 * 72000, SDS-PAGE
octamer
Serratia marcescens type S
-
8 * 72000, SDS-PAGE
-
polymer
-
12-16 * 45000, SDS-PAGE
tetramer
-
-
tetramer
-
4 * 48000, SDS-PAGE
tetramer
-
4 * 52000, SDS-PAGE
tetramer
-
2 * 35000 + 2 * 46000, heterodimer, SDS-PAGE
tetramer
Salmonella enterica subsp. enterica serovar Typhimurium HD11-AE2
-
4 * 54000, SDS-PAGE
-
monomer
Aspergillus fumigatus IFO5840
-
1 * 32000, SDS-PAGE
-
additional information
-
a monomer is a three-layered alpha/beta/alpha structure with a central beta sheet sandwiched on either side by alpha-helices
additional information
-
stabilized by a unique domain-swapping interaction between enzyme subunits, the active site is located in the mouth of the enzyme barrel
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
10 mg/ml purified recombinant His-tagged enzyme, vapour phase equilibration against 11-14% PEG 8000, 0.1 M HEPES, pH 7.3-7.7, 0.2 M MgCl2, in hanging drop geometry, flash-cooling in a buffer containing 30% v/v glycerol for cryoprotection, also crystallization of a seleno-methionine derivatized enzyme, X-ray diffraction structure determination and analysis at 1.5 A resolution
-
the structure of Zn-CDA is determined to a resolution of 1.7 A with phosphonocytosine a potent mimic of the putative tetrahedral intermediate bound in the active site
-
the wild type enzyme in complex with the mechanism-based inhibitors 4-(R)-hydroxyl-3,4-dihydropyrimidine or 5-fluoro-4-(S)-hydroxyl-3,4-dihydropyrimidine and the mutant enzyme V152A/F316C/D317G are crystallized by the sitting drop vapor diffusion method, using 10-15% (w/v) PEG 6K, 200 mM MgCl2 and 100 mM HEPES (pH 7-8)
-
wild-type enzyme and mutants D314G, D314A, D314S, free and in complex with mechanism-based inhibitor 5-fluoro-4-(S)-hydroxyl-3,4-dihydropyrimidine
-
crystallization strategy named microseed matrix screening, differential chelation pattern of cations by acidic surfaces of proteins within crystal lattice as a critical parameter of crystal nucleation and growth
-
molecular dynamics simulation of free enzyme and in complex with cytosine, uracil and reaction intermediates
-
PDB ID 1UAQ, structure analysis and comparison to the quantum mechanical/molecular mechanical molecular dynamics simulation model, overview
-
purified recombinant wild-type and selenomethionine-labeled enzymes in 10% 2-propanol, 20% PEG 4000, 0.1 M Na HEPES, pH 7.5, at 4C and at 22C by hanging drop vapour diffusion method, 0.002 ml of both reservoir and protein solution are mixed in presence of 2-hydroxypyrimidine, 3-5 days to 1-2 weeks at 22C, micro-seeding, X-ray diffraction structure determination and analysis at beyond 1.5 A resolution
-
recombinant A23L/D92E/V108I/I140L mutant bound to the transition state analogue, hanging drop vapour diffusion method, 2 days, crystals are soaked for 20 min in a mother liquor solution containing 2-hydroxypyrimidine concentrated 1.2:1 relative to protein, after soaking, the crystals are immediately transferred briefly to a cryo-buffer containing the 2-hydroxypyrimidine mother liquor plus 25% DMSO, X-ray diffraction structure determination and analysis at 2.3 A resolution, modelling and molecular replacement
-
the crystal structure of cytosine deaminase combined with the substrate uracil, PDB ID code: 1P6O, optimization in the water solvent at the ONIOM molecular dynamics study, overview
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9
-
stable in this range at 4C for at least 48 h
209484
5.5 - 8
-
-
209501
6 - 8
-
-
669819
8
-
-
209488
9 - 10
-
most stable at
209497
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
stable for a week
669819
37
-
the hyaluronan binding domain of tumor necrosis factor alpha-stimulated gene-6-cytosine deaminase fusion protein retains 20% of its initial enzyme activity after 24 h, 12% after 48 h, and 6% after 124 h at 37C. In contrast, the activity of cytosine deaminase decreases rapidly at 37C, and retains only about 5% of initial activity after 24 h
713064
42
-
the melting temperature of cytosine deaminase is at 42C
713064
45
-
extremely thermo-unstable, loses more than 85% activity when heated for 10 min at pH 7
209501
60
-
-
209497
60
-
thermostable between pH 7-9
209502
60
-
5 min, 70% residual activity
669819
70
-
after treating for 10 min at pH 7, 75% activity remains
209487
73
-
extremely thermostable
209503
75
-
75% activity remains after treatment for 10 min, pH 7
209488
75
-
still active at, able to withstand high temperature denaturation
209493
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
conjugation of poly-L-lysine to cytosine deaminase increases the enzyme's stability after uptake into cells, mechanism, overview
-
unstable in absence of reducing agents
-
exceptionally stable to denaturation
-
stable in cell-free extracts
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
stable
-
209488, 209490
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, pH 5.5-8.0, stable for at least 24 h
-
5C, loses 40% of its activity after 2 weeks, lost activity can be restored by treatment with 0.05 mM FeSO4
-
-15C stable for several months
-
4C, stable in the pH-range 5-9 for at least 48 h
-
4C, pH 6.5-9, no loss of activity over a 2 week period
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
-
recombinant enzyme as a mixture of Zn2+ and Fe2+ enzyme forms
-
gel filtration, SDS-PAGE
-
Ni2+-NTA column chromatography
-
recombinant His6-tagged yeast cytosine deaminase/single chain fragment variable human antibody fusion protein from Escherichia coli by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
FCA1 gene cloned from a genomic Candida albicans gene bank, constructed in the low-copy vector pMK122
-
CD gene codA cloned into mammalian expression vector, WiDr cells, a human CRC cell line transformed
-
CDase gene cloned into pBS+ vector, gentically engineered Escherichia coli strain that overexpresses the codBA operon on a multicopy plasmid
-
codBA operon encoding cytosine permease and cytosine deaminase cloned
-
development of an adenoviral vector for enzyme expression in cancer treatment by gene therapy, expression of the enzyme mutant D134A using this vector in human glioma cell lines D54MG, U87MG, and U251MG
-
enzyme expression in murine colorectal cancer cell line MC38; plasmid pBCMGSNeo/CD/CMV containing cytosine deaminase of Escherichia coli used for transfection of MC-38 cells
-
expressed in bone marrow-derived mesenchymal stem cells
Q6Q8Q1
expressed in Escherichia coli BL21(DE3) and BL21-RIL cells
-
expression in human cervical epithelial adenocarcinoma cell line HeLa, human pancreatic carcinoma cell line MIA PaCa-2, and human colon carcinoma cell lines WiDr and HT29
-
expression of a chimeric fusion protein consisting of cytosine deaminase and uracil phosphoribosyltransferase in human pancreatic cancer and glioma cell lines
-
expression of recombinant cytosine deaminase in Bifidobacterium breve I-53-8w using a shuttle plasmid Escherichia coli-Bifidobacterium, overview
-
expression of the enzyme from a replication-incompetent vector, comprising the cytosine deaminase gene and the L-plastin promoter, in human hepatocellular carcinoma cell lines HepG2, Chang Liver, Huh-7 and SK-Hep-1, expression analysis in the different cell lines, overview
-
expression of the enzyme in human and murine cancer cell lines and tumors using a herpes simplex type 1 virus, HSV-1, by exchanging the viral gamma1_34.5 gene for the cytosine deaminase CD gene, method development for the oncolytic HSV vector in gene therapy, overview
-
expression of the enzyme in Rattus norvegicus, BDIX rats, in induced colorectal adenocarcinoma in a gene therapy approach
-
expression of the fusion protein HSV-1TKglyCD in HEK-293 cells and in the human lung cancer cell line NCIH460
-
expression of the recombinant fusion gene from adenoviral vector under control of the human telomerase reverse transcriptase promoter in murine syngeneic MBT-2 bladder tumor cells, overview
-
pMP201 vector and derivatives with aminoglycoside resistance gene, synthetic version of the cytosine deaminase gene (CodA), optimized for expression in Streptomyces species, generation of Streptomyces lividans TK24 protoplasts, transformation of Streptomyces lividans
P25524
sucloning in strain JM109, construction of a shuttle plasmid Escherichia coli-Bifidobacterium longum, and expression in Bifidobacterium longum strain 105A, expression analysis
-
therapeutic CDase gene for human metastatic colorectal carcinoma
-
expression in Clostridium sp.
-
expressed in Escherichia coli BL21-Codon Plus (DE3)-RIPL cells
-
expression as fusion protein with uracil phosphoribosyltransferase in human pancreatic and colorectal cancer cell lines AsPC1, BxPC3, CaPan1, MIA PaCa2, Panc1, and HT-29, overview
Q12178
expression as His-tagged enzyme in Escherichia coli strain BL21 and as selenomethionine-labeled enzyme in strain B834
-
expression in Escherichia coli TG1, pQE30Xa plasmid
-
expression of the chimeric mutant cytosine deaminase/uracil phosphoribosyl transferase in Plasmodium falciparum, negative selection with 5-fluorocytosine
-
expression of the enzyme cloned in a construct comprising an SV40 minimal promoter and nine copies of a hypoxia-responsive element in Y87-1 and Y87-2 cells confering the 5-fluorocytosine hydrolyzing activity to the transformed cells, negative control are Z87 and U-87 MG cells, overview
-
expression of the fusion gene encoding the extracellular and transmembrane domains of the human nerve growth factor receptor and the cytoplasmic portion of the yeast CD gene in murine 4T1 breast carcinoma cells as cytosolic protein, which renders the cells highly sensitive to treatment by 5-fluorocytosine prodrug
-
expression of the His6-tagged yeast cytosine deaminase/single chain fragment variable human antibody fusion protein in Escherichia coli as soluble protein
-
expression of wild-type and mutant enzymes in Escherichia coli enzyme-deficient strain GIA39(DE3), genetic complementation assays, construction of mammalian expression vectors, overview
-
expression vector with cytosine deaminase fused to monomeric DsRed (mDsRed), expression vector contains immediate early promoter of cytomegalovirus (CMV) and a hygromycin B resistance gene, transient transfection of COS-7 cells
-
FCY1 gene cloned and characterized
-
stable transduction of human mesenchymal stem cells derived from adipose tissue (AT-MAS) with retroviral pST2 vector bearing yeast fusion cytosine deaminase, GP+E-86 cells and GP+envAM12 used as retroviral packaging mouse cell line, NIH-3T3 mouse fibroblast cells used for titration of viral inoculum
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S29L
-
the substitution in the cytosine deaminase Fca1p is responsible for clade-specific fluorocytosine resistance in Candida dubliniensis
S29L
Candida dubliniensis isolates SA113, SA109, Eg202, Eg204 and p7276
-
the substitution in the cytosine deaminase Fca1p is responsible for clade-specific fluorocytosine resistance in Candida dubliniensis
-
D134A
-
site-directed mutagenesis, the mutant enzyme shows a higher affinity for cytosine than the wild-type enzyme
D313A
-
metal contet: 0.57 Zn, 0.32 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
D313N
-
metal contet: 1.05 Zn, 0.05 Fe. kcat decreased compared to wild-type, Km increased compared to wild-type
D314A
-
11fold increase in KM-value with cytosine, decrease in KM-value with 5-fluorocytosine
D314A
-
impaired catalytic efficiency for cytosine, improved catalytic efficiency for 5-fluorocytosine
D314A
P25524
PCR-directed mutagenesis, activity against 5-fluorocytosine 2-fold increased, 17-fold lower sensitivity against native cytosine
D314E/F316L/D317G
-
the mutant displays 9% substrate specificity towards cytosine and 1820% substrate specificity towards 5-fluorocytosine compared to the wild type enzyme
D314G
-
impaired catalytic efficiency
D314S
-
impaired catalytic efficiency
E217A
-
metal contet: 0.9 Zn, 0.08 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
E217Q
-
metal contet: 0.87 Zn, 0.15 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
F310A
-
no activity with cytosine
F316A
-
KM-value with cytosine similar to wild-type, decrease in KM-value with 5-fluorocytosine
G311A
-
no activity with cytosine
H246A
-
metal contet: 0.59 Zn, 0.33 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
H246N
-
metal contet: 0.53 Zn, 0.29 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
H246Q
-
metal contet: 0.31 Zn, 0.33 Fe. kcat and Km decreased compared to wil-type
P318A
-
4fold increase in KM-value with cytosine
Q156A
-
metal contet: 0.92 Zn, 0.04 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
Q156N
-
metal contet: 1.40 Zn, 0.04 Fe. Mutant possesses less than 0.01% of activity of wild-type enzyme
V152A/F316C/D317G
-
the mutant displays 4% substrate specificity towards cytosine and 1920% substrate specificity towards 5-fluorocytosine compared to the wild type enzyme
V315A
-
no activity with cytosine
V315L/F316V/D317G
-
the mutant displays 6% substrate specificity towards cytosine and 1880% substrate specificity towards 5-fluorocytosine compared to the wild type enzyme
D314A
Escherichia coli K12
-
PCR-directed mutagenesis, activity against 5-fluorocytosine 2-fold increased, 17-fold lower sensitivity against native cytosine
-
C320A
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320D
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320F
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320K
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320L
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320Q
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320S
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320T
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320W
-
mutant shows anti-HIV-1 activity comparable to wild-type
C320Y
-
A3DE catalytic activity is significantly increased which in turn increases antiviral activity by more than 20fold
C320Y/E264Q
-
insertion of E264Q mutation completely disrupts C320Y activity, virion packaging capability is not impaired. Thus, the activity of C320Y does require an active cytidine deaminase
DELTA307
-
mutant shows disrupted anti-HIV activity
DELTA320
-
deletion mutant shows anti-HIV-1 activity comparable to wild-type
Y307A
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mutant shows disrupted anti-HIV activity
Y307C
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mutant shows disrupted anti-HIV activity
Y307K
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mutant shows disrupted anti-HIV activity
Y307R
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mutant shows disrupted anti-HIV activity
A23L/D92E/V108I/I140L
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construction of superimposed mutants by combining randomly generated single nucleotide mutants with the triple mutant, the superimposed mutant does not show enhanced activity with 5-fluorouracil and negates the effect introduced by the triple substitutions
A23L/I140L
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site-directed mutagenesis, the mutant display elevated unfolding temperatures in denaturation experiments and increased half-lives of catalytic activity at elevated temperatures, the mutant cells show an about 30% reduced sensitivity to 5-fluorouracil compared to the wild-type cells
A23L/M93L/V108I/I140L
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construction of superimposed mutants by combining randomly generated single nucleotide mutants with the triple mutant, the superimposed mutant does not show enhanced activity with 5-fluorouracil and negates the effect introduced by the triple substitutions
A23L/V108I/I140L
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site-directed mutagenesis, display elevated unfolding temperatures in denaturation experiments and increased half-lives of catalytic activity at elevated temperatures, the mutant cells show an about 50% reduced sensitivity to 5-fluorouracil compared to the wild-type cells
A23L/V108I/I140L/I98L
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construction of superimposed mutants by combining randomly generated single nucleotide mutants with the triple mutant, the superimposed mutant does not show enhanced activity with 5-fluorouracil and negates the effect introduced by the triple substitutions
D92E
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random mutagenesis, the mutation is located at the enzyme's dimer interface, the mutant shows increased thermal stability with elevated Tm values and increased activity half-life compared to the wild-type enzyme, the mutant cells show an about 30% reduced sensitivity to 5-fluorouracil compared to the wild-type cells
E64A
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the mutant lacks enzyme activity
E64A
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E64A mutation causes a decrease in kcat of 5 orders of magnitude and an increase in Km of 2 orders of magnitude, resulting in a decrease in kcat/Km of 8 orders of magnitude
H312A
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3fold increase in KM-value with cytosine
additional information
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construction of secreted form of enzyme by fusion with pre-prosegment of human tissue plasminogen activator. Secreted enzyme temporarily spares transduced cells and enhanced accumulation of extracellular 5-fluorouracil. Tumors expressing the secreted enzyme have an improved response to 5-fluorocytosine treatment compared to tumors expressing intracellular enzyme
additional information
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adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts, overview
additional information
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construction of a chimeric fusion protein consisting of cytosine deaminase and uracil phosphoribosyltransferase in human pancreatic cancer and glioma cell lines, the recombinant fusion enzyme mediates 5-fluorouracil cell killing and leads to growth inhibition of tumor tissue, overview
additional information
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construction of a fusion gene in an adenoviral vector comprising human telomerase reverse transcriptase promoter, and cytosine deaminase from Escherichia coli
additional information
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construction of a fusion gene using cytosine deaminase in combination with uracil phosphoribosyl transferase, the product of the suicide gene, CDUPRT, converts the prodrug, 5-fluorocytosine, into 5-fluorouracil and other cytotoxic metabolites that kill both CDUPRT-expressing and surrounding cells, via a bystander effect, in pseudo-metastates in mouse tissues, tissue-specifix effects, overview
additional information
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construction of a fusion protein HSV-1TKglyCD combining Herpes simplex virus type-1 thymidine kinase, HSV-1TK, and Escherichia coli cytosine deaminase, CD, with screening for the optimal suitable linker peptide, molecular modeling, overview
additional information
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construction of a replication-incompetent vector, i.e. AdLPCD vector, comprising the cytosine deaminase gene and the L-plastin promoter, which regulates the expression of transgenes
additional information
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construction of and transfection with vectors encoding Escherichia coli cytosine deaminase and herpes simplex virus thymidine kinase leads to greater cell death in procaspase-3-expressing clones of 3AO cells, ovarian cancer cells than in control cells after treatment with ganciclovir or 5-fluorocytosine, as well as more rapid activation of caspase-3 and more rapid cleavage of poly (adenosine diphosphate-ribose) polymerase, overview
additional information
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expression of recombinant cytosine deaminase activity in Bifidobacterium breve I-53-8w is eefective in tumor-targeting enzyme/prodrug therapy in rats, phenotype, overview
additional information
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expression of recombinant cytosine deaminase activity in Bifidobacterium longum results in and strong enhancement of tumor-targeting enzyme/prodrug therapy in human cells, overview
additional information
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expression of the enzyme in Rattus norvegicus, BDIX rats, in induced colorectal adenocarcinoma in a gene therapy approach leads to intratumor chemotherapy using 5-fluorocytosine, which is locally converted to 5-fluorouracil, the treatment results in destruction of the gene-modified tumor, other physiological processes might contribute to the tumor destruction, overview
E64D
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the effect of E64D mutation are slightly milder than the E64A mutation
additional information
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co-expression of the uracil phosphoribosyltransferase gene with a chimeric truncated human nerve growth factor receptor/cytosine deaminase fusion gene, using a single retroviral vector, augments cytotoxicity of transduced human T cells exposed to 5-fluorocytosine, for positive selection, overview, construct NG/CDiU expressing UPRT and NG/CD, using a bicistronic message, provides the greatest UPRT activity and killing, reducing the lethal dose of 5-FC sufficient to eradicate 90% of cells
additional information
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construction of a chimeric bifuntional enzyme comprising cytosine deaminase and uracil phosphoribosyl transferase activities, overview
additional information
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construction of a fusion gene consisting of the SV40 minimal promoter, nine copies of a hypoxia-responsive element, and the yeast CD gene
additional information
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construction of a fusion gene encoding the extracellular and transmembrane domains of the human nerve growth factor receptor and the cytoplasmic portion of the yeast CD gene
additional information
Q12178
construction of a fusion protein of yeast cytosine deaminase with yeast uracil phosphoribosyltransferase
additional information
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construction of a His6-tagged fusion protein using the yeast cytosine deaminase and a single chain fragment variable human antibody specific for carcinoembryonic antigen, CEA, cell surfaces under control of the lac promoter, the chimeric enzyme shows high affinity for binding to Mel P5 and LoVo melanoma cells and improves tumor-selective prodrug activation, overview
additional information
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fusion of the HSV-1 tegument protein vp22, as full-length protein and as truncated protein lacking the trafficking residues, to cytosine deaminase and stable expression in 9L tumors confers enhanced bystander effect and increased therapeutic benefit in cancer gene therapy, overview
additional information
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to create enzyme variants with increased activity to 5-fluorocytosine, 11 codons within the most conserved region of the enzyme, T83, L84, Y85, T86, L88, S89, D92, M93, T95, G96, and I98 are subjected to regiospecific, partially randomizing mutagenesis, Absolutely conserved residues, T87, P90, C91, and C94, within this same region, assumed to be critical for activity, are omitted from randomization, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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facilitate pharmacological advance, possible application is transfer of FCY1 and FCA1 to mammalian cells naturally lacking enzyme activity, these genes should confer lethal sensitivity to 5-fluorocytosine
medicine
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treatment of cancer by infecting or implanting cytosine deaminase capsules near the tumor of a cancer patient
medicine
Chromobacterium violaceum YK 391
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treatment of cancer by infecting or implanting cytosine deaminase capsules near the tumor of a cancer patient
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biotechnology
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a chitosan-entrapped cytosine deaminase nanocomposite is developped. Sustained release of cytosine deaminase from the nanocomposite up to one week depicts its potential implication in prodrug inducted enzyme therapy
medicine
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oral 5-fluorocytosine in combination with selective delivery of CDase to cancerous cells by selectively introducing the bacterial CDase gene into the genome
medicine
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gene therapy for treatment of primary and metastatic tumors in the liver, development of gene therapy treatment for metastatic colorectal carcinoma
medicine
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new approach to chemotherapy of cancer, using substrate 5-fluorocytosine orally and enzyme capsules implanted locally, using conversion of product 5-fluorouracil, a potent antineoplastic substance, which is strongly toxic for mammalian cells as chemotherapeutic tool against tumors, enzyme/prodrug gene therapy, artificial gene composed for metastatic colorectal carcinoma
medicine
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enzyme is of interest both for antimicrobial drug design and for gene therapy applications against tumors
medicine
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construction of secreted form of enzyme by fusion with pre-prosegment of human tissue plasminogen activator. Secreted enzyme temporarily spares transduced cells and enhanced accumulation of extracellular 5-fluorouracil. Tumors expressing the secreted enzyme have an improved response to 5-fluorocytosine treatment compared to tumors expressing intracellular enzyme
medicine
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mutant enzyme with improved activity towards cancer prodrug 5-fluorouracil for suicide gene therapy
medicine
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establishment of a hypoxia-dependent prodrug-activating system using the enzyme cloned into a hypoxia-targeted adenoviral vector, overview
medicine
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the enzyme is useful in gene therapy for treatment of cancer, bladder tumor model, overview
medicine
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the enzyme is useful in gene therapy of cancers, conjugation of poly-L-lysine to cytosine deaminase improves the efficacy of enzyme/prodrug cancer therapy, overview
medicine
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the enzyme is useful in treatment of human ovarian cancer by genetic prodrug activation therapy, overview
medicine
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cytosine deaminase is used in combination with 5-fluorocytosine as an enzyme-prodrug combination for targeted genetic cancer treatment
medicine
Q6Q8Q1
the cytosine deaminase-human mesenchymal stem cell/5-fluorocytosine system is a potential molecular chemotherapeutic tool for cancer treatment
pharmacology
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exogenous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme/prodrug therapy, overview
pharmacology
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the recombinant fusion enzyme HSV-1TKglyCD might be useful in cancer gene therapy
pharmacology
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applicability of gene-directed enzyme prodrug therapy (GDEPT), prodrug encapsulation in liposomes, liposomal 5-fluorocytosine (5-FC) achieves high local concentration for suicide therapy
pharmacology
P25524
negative selection system for actinobacteria based on cytosine deaminase
pharmacology
Escherichia coli K12
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negative selection system for actinobacteria based on cytosine deaminase
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diagnostics
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the enzyme, expressed by Clostridium sp., can be used for detection of Clostridia-containing tumors in humans using clostridial directed 5-fluorouracil prodrug therapy
medicine
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efficiency of liposome-mediated cytosine deaminase suicide gene therapy can be improved by radiation. With HR-8348 tumor xenograft model, tumor volume is inhibited by 81.5%, 48.5%, and 37.5%, in the combined enzyme/5-fluorocytosine with radiation group, enzyme/5-fluorocytosine group and radiation group, and the wet weight of tumor is decreased by 80%, 41.7%, and 37.7%, resp.
medicine
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inhibition of tumor growth in mice treated with gene transfer of interleukin IL-12 plus enzyme/5-fluorcytosine is significantly greater than in mice treated with enzyme or IL-12 alone. Combined gene transfer increases splenic natural killer cell activity and interferon-gamma production by slenocytes and increases tumor growth inhibition and mean animal survival time
analysis
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crystallization strategy named microseed matrix screening, differential chelation pattern of cations by acidic surfaces of proteins within crystal lattice as a critical parameter of crystal nucleation and growth
medicine
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facilitate pharmacological advance, possible application is transfer of FCY1 and FCA1 to mammalian cells naturally lacking enzyme activity, these genes should confer lethal sensitivity to 5-fluorocytosine
medicine
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enzyme is interesting for anticancer gene therapy since it deaminates the prodrug 5-fluorocytosine to the active drug 5-fluorouracil
medicine
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cytosine deaminase gene therapy combined with radiation treatment in breast carcinoma bone tumor, which is painful and causes osteolysis, is evaluated in a 4T1murine breast carcinoma model, overview
medicine
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hypoxia-inducible cytosine deaminase/5-fluorocytosine therapy in combination with radiation therapy shows both a pronounced bystander effect and a radiosensitizing effect under hypoxic conditions
medicine
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the hyaluronan binding domain of tumor necrosis factor alpha-stimulated gene-6-cytosine deaminase fusion protein is an alternative to antibody-directed prodrug enzyme therapy approaches for cancer treatment
medicine
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efficiency of gene-directed enzyme/prodrug therapy (GDEPT) based on combination of fusion yeast cytosine deaminase (yCD) and 5-fluorocytosine (5FC) on model human medullary thyroid carcinoma (MTC) cell line TT is determined. Significant bystander effect is shown in vitro and 5-fluorocytosine administration results in potent antitumor effect in vivo. In addition high efficiency of cell-mediated GDEPT is shown, when human mesenchymal stromal cells are used as delivery vehicles in direct cocultures in vitro
pharmacology
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applicability of gene-directed enzyme prodrug therapy using the capability of human adipose tissue-derived mesenchymal stem cells (AT-MSC) as cellular vehicles expressing cytosine deaminase, CDy-AT-MSC/5FC-system, analyzed in cell lines and xenografts
pharmacology
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applicability of gene-directed enzyme prodrug therapy, feasibility of using magnetic resonance spectroscopy and optical imaging to measure non-invasively expression and function of cytosine deaminase in a preclinical tumor model
pharmacology
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cancer chemotherapy, antibody-directed enzyme-prodrug therapy (GDEPT/ADEPT), biopanning assay