Application | Comment | Organism |
---|---|---|
medicine | even slight alterations in the active site pocket of AGT do not prevent its ability to protect cells from alkylating agents, can block the paradoxical enhancement of the genotoxicity of the larger alpha,omega-dihaloalkanes by reducing the reaction with Cys145 | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant AGT and mutants expressed in Escherichia coli, pQE expression vectors for wild-type and mutant AGT production and plasmid pREP4 cotransformed into TRG8 cells to suppress basal AGT protein expression | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
G156A | 40% reduced ability of the protein to react with Br(CH2)2Br | Homo sapiens |
G160R | 28% reduced ability of the protein to react with Br(CH2)2Br | Homo sapiens |
P140A | 70% reduced ability of the protein to react with Br(CH2)2Br | Homo sapiens |
P140K | 95% reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity, no change in the stability of the AGT-Cys145S-(CH2)2Br intermediate | Homo sapiens |
R128A | substantially reduced AGT-mediated increase in toxicity and the induction of mutations in Escherichia coli cells treated with Br(CH2)2Br, is able to react with Br(CH2)2Br at the Cys145 acceptor site, but the resulting AGT-Cys145S-(CH2)2Br is much less able to produce a covalent adduct with DNA | Homo sapiens |
Y114A | reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity | Homo sapiens |
Y114E | substantially reduced AGT-mediated increase in toxicity and the induction of mutations in Escherichia coli cells treated with Br(CH2)2Br | Homo sapiens |
Y158H | 78% reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity, no change in the stability of the AGT-Cys145S-(CH2)2Br intermediate | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
Br(CH2)2Br | inactivates purified AGT and mutant R128A to approximately the same extent; inactivates purified AGT and mutant R128A to approximately the same extent, small reduction in the loss of activity in the absence of DNA, but no effect at all in the presence of DNA, inactivates mutant Y114A much less than wild-type, and DNA completely prevents this inactivation, mutants P140K and Y158H are less inactivated than wild-type AGT, specifically in the presence of DNA | Homo sapiens | |
Br(CH2)3Br | mutant P140K requires higher concentrations than wild-type AGT for inactivation | Homo sapiens | |
Br(CH2)5Br | mutant P140K requires higher concentrations than wild-type AGT for inactivation | Homo sapiens | |
BrCH2Br | wild-type AGT and mutant P140K show no difference in sensitivity to BrCH2Br | Homo sapiens | |
O6-benzylguanine | mutants P140K and Y158H are the most resistant | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
AGT | - |
Homo sapiens |
O6-alkylguanine-DNA alkyltransferase | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0001 | - |
wild-type | Homo sapiens | O6-benzylguanine | |
0.004 | - |
mutant P140A | Homo sapiens | O6-benzylguanine | |
0.005 | - |
mutant G160R | Homo sapiens | O6-benzylguanine | |
0.015 | - |
mutant G156A | Homo sapiens | O6-benzylguanine | |
0.62 | - |
mutant Y158H | Homo sapiens | O6-benzylguanine | |
1.2 | - |
mutant P140K | Homo sapiens | O6-benzylguanine |