Application | Comment | Organism |
---|---|---|
drug development | design and synthesis of the inhibitors targeting NTMT1 as potential therapeutics in cancer treatment | Homo sapiens |
pharmacology | NTMT1 inhibitors can be potential anticancer therapeutics | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | 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 | Homo sapiens | |
NAM-TZ-SPKRIA | the inhibitor is enzyme-specific with a competitive inhibition pattern for both substrates, selective versus protein lysine methyltransferase G9a and arginine methyltransferase 1. The inhibitor substantially suppresses the methylation progression. The sulfur is replaced with a less reactive nitrogen to yield N-adenosyl-L-methionine as a stable analogue of S-adenosyl-L-methionine. Hexapeptide SPKRIA is derived from the N-terminus of regulator of chromosome condensation 1, RCC1. Binding structure modeling using the crystal structure of NTMT1 with S-adenosyl-L-homocysteine, PDB ID 2EX4. The two parts are connected via the triazole linker. NAM-TZ-SPKRIA acts as a competitive inhibitor when the concentration of S-adenosyl-L-methionine is varied from 0.003-0.010 mM and RCC1-10 substrate peptide is at a fixed concentration at 0.003 mM | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | the protein N-terminal methyltransferase 1 (NTMT1) methylates the alpha-N-terminal amines of proteins | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
additional information | NTMT1 is upregulated in a variety of cancers | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
3 S-adenosyl-L-methionine + N-terminal-SPKRIA-[RCC1] | i.e. regulator of chromosome condensation 1 | Homo sapiens | 3 S-adenosyl-L-homocysteine + N-terminal-trimethyl-SPKRIA-[RCC1] | - |
? | |
additional information | the protein N-terminal methyltransferase 1 (NTMT1) methylates the alpha-N-terminal amines of proteins | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
NTMT1 | - |
Homo sapiens |
protein N-terminal methyltransferase 1 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | - |
Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | steady-state inhibition of NTMT1 by NAM-TZ-SPKRIA, kinetic analysis | Homo sapiens | |
0.0002 | - |
NAM-TZ-SPKRIA | pH and temperature not specified in the publication | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0013 | - |
pH and temperature not specified in the publication | Homo sapiens | NAM-TZ-SPKRIA |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | NTMT1 is upregulated in a variety of cancers | up |
General Information | Comment | Organism |
---|---|---|
malfunction | NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects | Homo sapiens |