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Literature summary for 2.1.1.244 extracted from

  • Zhang, G.; Richardson, S.L.; Mao, Y.; Huang, R.
    Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors (2015), Org. Biomol. Chem., 13, 4149-4154.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.244

Application

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

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/ Products (Substrates)

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 ?
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 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information NTMT1 is upregulated in a variety of cancers Homo sapiens
-

Substrates and Products (Substrate)

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]
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 ?
additional information the protein N-terminal methyltransferase 1 (NTMT1) methylates the alpha-N-terminal amines of proteins Homo sapiens ?
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 ?

Synonyms

Synonyms Comment Organism
NTMT1
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 Homo sapiens
protein N-terminal methyltransferase 1
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 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
 Homo sapiens

Ki Value [mM]

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 IC50 Value Maximum Comment Organism Inhibitor Structure
0.0013
-
 pH and temperature not specified in the publication Homo sapiens NAM-TZ-SPKRIA

Expression

Organism Comment Expression
Homo sapiens NTMT1 is upregulated in a variety of cancers up

General Information

General Information Comment Organism
malfunction NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects Homo sapiens