BRENDA - Enzyme Database show

Target enzyme mutations are the molecular basis for resistance towards pharmacological inhibition of nicotinamide phosphoribosyltransferase

Olesen, U.; Petersen, J.; Garten, A.; Kiess, W.; Yoshino, J.; Imai, S.; Christensen, M.; Fristrup, P.; Thougaard, A.; Björkling, F.; Jensen, P.; Nielsen, S.; Sehested, M.; BMC Cancer 10, 677 (2010)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
2.4.2.12
expressed in Escherichia coli Rosetta 2 (DE3)
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
2.4.2.12
DELTA D93
naturally occuring mutation in CHS-828 or APO866 resistant cell lines, about 20% of wild type aczivity
Homo sapiens
2.4.2.12
H191R
activity reduced by about 50%
Homo sapiens
2.4.2.12
H191R/K342R
naturally occuring mutation in APO866 resistant cell line
Homo sapiens
2.4.2.12
H191R/K342R/Q388R
naturally occuring mutation in TP201565 resistant cell line
Homo sapiens
2.4.2.12
K342R
naturally occuring mutation, activity reduced by about 50%
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.2.12
CHS-828
competitive inhibitor
Homo sapiens
2.4.2.12
FK-866
-
Homo sapiens
2.4.2.12
TP201565
competitive inhibitor
Homo sapiens
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.4.2.12
Homo sapiens
P43490
-
-
Purification (Commentary)
EC Number
Commentary
Organism
2.4.2.12
immobilized metal ion affinity chromatography (Ni2+)
Homo sapiens
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
2.4.2.12
HCT-116 cell
-
Homo sapiens
-
2.4.2.12
HEK-293T cell
-
Homo sapiens
-
2.4.2.12
NYH cell
-
Homo sapiens
-
2.4.2.12
PC-3 cell
-
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.2.12
nicotinamide + 5-phosphoribosyl 1-diphosphate
-
721934
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
?
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.4.2.12
0.00011
-
wild type protein, pH 8.5, 37°C
Homo sapiens
FK-866
2.4.2.12
0.008585
-
H191R mutant protein, pH 8.5, 37°C
Homo sapiens
FK-866
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
2.4.2.12
expressed in Escherichia coli Rosetta 2 (DE3)
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
2.4.2.12
DELTA D93
naturally occuring mutation in CHS-828 or APO866 resistant cell lines, about 20% of wild type aczivity
Homo sapiens
2.4.2.12
H191R
activity reduced by about 50%
Homo sapiens
2.4.2.12
H191R/K342R
naturally occuring mutation in APO866 resistant cell line
Homo sapiens
2.4.2.12
H191R/K342R/Q388R
naturally occuring mutation in TP201565 resistant cell line
Homo sapiens
2.4.2.12
K342R
naturally occuring mutation, activity reduced by about 50%
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.4.2.12
0.00011
-
wild type protein, pH 8.5, 37°C
Homo sapiens
FK-866
2.4.2.12
0.008585
-
H191R mutant protein, pH 8.5, 37°C
Homo sapiens
FK-866
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.2.12
CHS-828
competitive inhibitor
Homo sapiens
2.4.2.12
FK-866
-
Homo sapiens
2.4.2.12
TP201565
competitive inhibitor
Homo sapiens
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
2.4.2.12
immobilized metal ion affinity chromatography (Ni2+)
Homo sapiens
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
2.4.2.12
HCT-116 cell
-
Homo sapiens
-
2.4.2.12
HEK-293T cell
-
Homo sapiens
-
2.4.2.12
NYH cell
-
Homo sapiens
-
2.4.2.12
PC-3 cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.2.12
nicotinamide + 5-phosphoribosyl 1-diphosphate
-
721934
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
?