EC Number   |
Inhibitors |
Structure |
|---|
   2.1.1.244 | 5'-([3-[(2S)-2-acetylpyrrolidin-1-yl]propyl][(3S)-3-amino-3-carboxypropyl]amino)-5'-deoxyadenosine |
- |
   |
| 2.1.1.244 | me3-RCC1-6 |
product inhibition |
|
| 2.1.1.244 | more |
the inhibition patterns indicate a rapid equilibrium random kinetic mechanism |
|
| 2.1.1.244 | more |
feasibility of using a triazole group to link an S-adenosyl-L-methionine analogue with a peptide substrate to construct bisubstrate analogues as NTMT1 potent and selective inhibitors, a general strategy for the development of selective protein methyltransferase inhibitors |
|
| 2.1.1.244 | more |
development of potent and specific inhibitors, bisubstrate analogues that simultaneously target both binding sites are proven to be an effective strategy to obtain potent and selective inhibitors for many enzymes with two binding sites. Because NTMT1 forms a ternary complex during catalysis, a bisubstrate strategy has been applied to design and synthesize bisubstrate inhibitors by covalently linking a SAM analogue with a peptide substrate to mimic the transition state. NTMT1 bisubstrate inhibitors contain three components: an N-adenosyl-L-methionine (NAM) that replaces the sulfonium ion of SAM with a nitrogen atom, a hexapeptide derived from the N-terminal sequence of NTMT1 substrate, and a linker. The potency of such bisubstrate inhibitors corroborate the Bi Bi mechanism of NTMT1 methylation |
|
| 2.1.1.244 | N-terminal-acetyl-SPKRIAKRRS-[RCC1] |
noncompetitive versus S-adenosyl-L-methionine and protein substrate |
|
| 2.1.1.244 | N-terminal-trimethyl-SPKRIA-[RCC1] |
product inhibition, competitive inhibitor versus protein substrate, noncompetitive versus S-adenosyl-L-methionine |
|
| 2.1.1.244 | NAM-C3-GPRRRS |
GPKRRS peptide derived from CENP-A is linked through a propylene group |
|
| 2.1.1.244 | NAM-C3-GPRRRS |
- |
|
| 2.1.1.244 | NAM-C3-PKRIA-NH2 |
discovery of the potent NTMT1 bisubstrate inhibitor NAM-C3-PKRIA-NH2 that exhibits greater than 100fold selectivity against a panel of methyltransferases. Crystal structure analysis of NTMT1 in complex with the inhibitor reveals that NAM-C3-PKRIA-NH2 occupies substrate and cofactor binding sites of NTMT1 |
|
