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Information on EC 3.5.4.1 - cytosine deaminase
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3.5.4.1 cytosine deaminaseIUBMB Comments
Also acts on 5-methylcytosine.
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Word Map
- 3.5.4.1
- cytidine
- deaminases
- 5-fluorocytosine
-
deamination
-
prodrugs
- virion
-
hypermutation
- viruses
- 5-fluorouracil
- retroviruses
-
suicide
-
apolipoprotein
-
retroviral
- uracil
-
single-stranded
-
apobecs
-
antiretroviral
-
polypeptide-like
-
mrna-editing
-
g-to-a
-
bystander
-
proviral
-
retroelements
-
anti-hiv-1
-
activation-induced
- lentiviruses
-
retrotransposons
- deoxycytidine
- ganciclovir
-
encapsidation
-
retrotransposition
- ssdna
-
hsv-tk
-
line-1
- sivmac
- medicine
-
gene-directed
- fiv
-
minus-strand
-
cullin
- samhd1
- vpr
-
replication-competent
-
single-cycle
-
gdept
-
nickase
- agriculture
- biotechnology
-
elongins
- analysis
-
xenotropic
- proviruses
- pharmacology
- diagnostics
-
non-ltr
- molecular biology
- trim5alpha
The enzyme appears in viruses and cellular organisms
Synonyms
A3DE, APOBEC1, APOBEC3, APOBEC3G, CD, CDA, CDase, codA, CodA protein, Cytosine aminohydrolase, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
APOBEC3
CD
CDA
CDase
codA
Cytosine aminohydrolase
-
-
-
-
cytosine deaminase
cytosine deaminase I
cytosine deaminase II
cytosine deaminase S
Fca1p
FCY1
isocytosine deaminase
-
-
-
-
yCD
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytosine + H2O = uracil + NH3
-
-
-
-
cytosine + H2O = uracil + NH3
active site architecture and substrate binding, catalytic mechanism
cytosine + H2O = uracil + NH3
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
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
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
cytosine aminohydrolase
Also acts on 5-methylcytosine.
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CAS REGISTRY NUMBER
COMMENTARY
9025-05-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
cytidine + H2O
1-beta-D-ribofuranosylpyrimidin-2(1H)-one + NH3
-
-
-
-
?
pyrimidin-2-one + H2O
(4R)-hydroxyl-3,4-dihydropyrimidine + ?
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
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
209493, 209496, 209497, 209502, 209503, 209507, 209508, 667616, 670746, 684772, 685669, 685673, 685848, 685938, 687168, 688280, 688927, 711669, 719155
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
-
recombinant enzyme in transfected cells, cytotoxic effects of the enzyme expressed form the AdLPCD vector, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
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
-
activation of the prodrug
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
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
-
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
-
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
used as negative selection marker system, increased 5-fluorocytosine sensitivity in Streptomyces lividans
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
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
-
recombinant enzyme expressed in Clostridium sp.
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
activation of the prodrug 5-fluorocytosine to the anticander drug 5-fluorouracil
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
release of 5-fluorouracil is rate-limiting and may involve multiple steps
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
activation of the prodrug by the recombinant fusion enzyme, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
recombinant enzyme in gene therapy in human glioblastoma cell lines Y87-1 and Y87-2
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
activation of the prodrug
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
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
activation of the prodrug, 5-fluorouracil is an inhibitor of DNA synthesis and RNA function
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
-
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
-
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
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
recombinant cytosine deaminase in gene therapy, expression and function in transgenic cell lines and xenograft tumors
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
recombinant enzyme in gene therapy, expression analysis in transgenic mice with xenograft tumors, optical imaging technologies
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
-
-
-
-
?
5-methylcytosine + H2O
thymine + NH3
-
-
-
-
?
creatinine + H2O
N-methylhydantoin + NH3
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
137029, 209484, 209487, 209488, 209489, 209493, 209496, 209497, 209498, 209502, 209503, 209504, 209505, 209506, 209507, 209508, 667616, 670746, 675179, 684772, 685669, 685673, 685848, 685938, 687168, 688280, 688927, 711669, 718902, 719155
-
-
?
cytosine + H2O
uracil + NH3
-
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
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
209484, 209485, 209486, 209487, 209488, 209489, 209492, 209493, 209494, 209495, 209497, 209501, 209506, 209507, 209508, 654095, 667664, 673932, 685615, 685937, 687192, 688612, 713064
-
-
?
cytosine + H2O
uracil + NH3
-
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
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
-
molecular dynamics study of the ligand release path in yeast cytosine deaminase, the active site is well protected by the C-terminal helix, residues 150Ć¢ĀĀ158, and F-114 loop, residues 111Ć¢ĀĀ117, substrate binding structure, overview
-
-
?
cytosine + H2O
uracil + NH3
-
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
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
-
-
?
additional information
?
-
-
no substrate: 5-azacytosine
-
-
?
additional information
?
-
enzyme is an important member of the pyrimidine salvage pathway
-
-
?
additional information
?
-
-
enzyme is an important member of the pyrimidine salvage pathway
-
-
?
additional information
?
-
-
creatinine is a poor substrate for Zn2+CDase and apoCDase
-
-
?
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
?
-
-
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 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
?
-
-
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
?
-
-
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 rate-determining step of the reaction concerns the breaking of the product-metal binding state and has a barrier of about 18 kcal/mol. The protonation of cytosine by Glu64 in the substrate binding stage as well as the product transport step are also important and influence the whole catalytic efficiency, due to their considerable barriers (12-13 kcal/mol). The driving force for the overall enzymatic reaction likely comes from the reactant delivery to the active site of the protein
-
-
?
additional information
?
-
-
the rate-determining step of the reaction concerns the breaking of the product-metal binding state and has a barrier of about 18 kcal/mol. The protonation of cytosine by Glu64 in the substrate binding stage as well as the product transport step are also important and influence the whole catalytic efficiency, due to their considerable barriers (12-13 kcal/mol). The driving force for the overall enzymatic reaction likely comes from the reactant delivery to the active site of the protein
-
-
?
additional information
?
-
the rate-determining step of the reaction concerns the breaking of the product-metal binding state and has a barrier of about 18 kcal/mol. The protonation of cytosine by Glu64 in the substrate binding stage as well as the product transport step are also important and influence the whole catalytic efficiency, due to their considerable barriers (12-13 kcal/mol). The driving force for the overall enzymatic reaction likely comes from the reactant delivery to the active site of the protein
-
-
?
additional information
?
-
-
5-methylcytosine, cytidine, deoxycytidine and CMP are no substrates
-
-
?
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
?
-
-
5-methylcytosine, cytidine, 5'-CMP, adenine, adenosine, 5'-AMP, guanine, guanosine, 5'-GMP and GMP are no substrates
-
-
?
additional information
?
-
-
5-methylcytosine, cytidine, 5'-CMP, adenine, adenosine, 5'-AMP, guanine, guanosine, 5'-GMP and GMP are no substrates
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
-
recombinant enzyme in transfected cells, cytotoxic effects of the enzyme expressed form the AdLPCD vector, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
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
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
used as negative selection marker system, increased 5-fluorocytosine sensitivity in Streptomyces lividans
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
activation of the prodrug 5-fluorocytosine to the anticander drug 5-fluorouracil
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
activation of the prodrug by the recombinant fusion enzyme, overview
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
inside a cell, cytosine and 5-fluorocytosine compete for the active site of the enzyme
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
-
recombinant enzyme in gene therapy in human glioblastoma cell lines Y87-1 and Y87-2
-
-
?
5-fluorocytosine + H2O
5-fluorouracil + NH3
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
-
-
?
cytosine + H2O
uracil + NH3
-
-
137029, 209484, 209487, 209488, 209489, 209493, 209496, 209497, 209498, 209502, 209503, 209504, 209505, 209506, 209507, 209508, 675179, 684772, 685669, 685673, 685848, 685938, 687168, 688280
-
-
?
cytosine + H2O
uracil + NH3
-
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
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
209484, 209485, 209486, 209487, 209488, 209489, 209492, 209493, 209494, 209495, 209497, 209501, 209506, 209507, 209508, 654095, 673932, 685615, 685937, 687192, 688612, 713064
-
-
?
cytosine + H2O
uracil + NH3
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
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
-
-
?
cytosine + H2O
uracil + NH3
-
-
-
-
?
additional information
?
-
enzyme is an important member of the pyrimidine salvage pathway
-
-
?
additional information
?
-
-
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
?
-
-
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 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
?
-
-
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
?
-
-
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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
BaCl2
CaCl2
Fe2+
FeCl3
MnCl2
Zn2+
Fe2+
bound to the active site, the metal ion coordinates a hydroxyl nucleophile, binding structure, overview
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+
-
ligands are two cysteines, a histidine, and one water molecule
Zn2+
residues His62, Cys91, and Cys94 are very important in coordinating the zinc cation
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
orotidine-5'-monophosphate
-
-
2-hydroxypyrimidine
binding structure modeling, inhibition mechanism, acts as a transition state analogue
Cu2+
-
-
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-chloromercuribenzoate
-
complete inhibition, reversed by cytosine, cysteine, dithiothreitol or 2-mercaptoethanol
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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%
dGMP
-
1.0 mM, substrate cytosine, relative activity 109%
ATP
-
1.0 mM, substrate cytosine, relative activity 105%, substrate 5-methylcytosine relative activity 113%
L-aspartic acid
-
10.0 mM, relative activity 158%
L-Glutamic acid
-
10.0 mM, relative activity 135%
L-hydroxyproline
-
10.0 mM, relative activity 141%
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
-
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
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.16
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
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 37ĆĀ°C
0.51
5-fluorocytosine
-
recombinant cytosine deaminase, in PBS buffer, pH not specified in the publication, at 37ĆĀ°C
3.76
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
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
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
0.46
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
1.65
cytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
3.16
cytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
4.9
cytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
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
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
17
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
19.71
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
83.68
5-fluorocytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
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
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
49.68
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000014
5-fluorocytosine
-
mutant E64A, pH 7.5, temperature not specified in the publication
0.00026
5-fluorocytosine
-
mutant E64D, pH 7.5, temperature not specified in the publication
5.24
5-fluorocytosine
-
wild type enzyme, pH and temperature not specified in the publication
8.02
5-fluorocytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
12.44
5-fluorocytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
15.27
5-fluorocytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
106
5-fluorocytosine
-
wild-type, pH 7.5, temperature not specified in the publication
0.35
cytosine
-
mutant enzyme V152A/F316C/D317G, pH and temperature not specified in the publication
0.94
cytosine
-
mutant enzyme V315L/F316V/D317G, pH and temperature not specified in the publication
1.29
cytosine
-
mutant enzyme D314E/F316L/D317G, pH and temperature not specified in the publication
106.8
cytosine
-
wild type enzyme, pH and temperature not specified in the publication
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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
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.1
0.22
2.6
2.7
3.1
87
additional information
additional information
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
-
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
-
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
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
-
pH-indicator assay for the measurement of the steady-state kinetic parameters of deamination reaction
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
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
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
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
-
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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
8.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Pseudomonas schuylkilliensis
Pseudomonas trifolii
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)
-
-
brenda
-
137029, 209484, 209487, 209488, 209489, 209493, 209498, 209503, 209504, 209505, 209506, 209507, 209508
-
-
brenda