6DTN

The structure of NTMT1 in complex with compound DC100-1

Summary for 6DTN

• Entry DOI: 10.2210/pdb6dtn/pdb
• Related PRD ID: PRD_002319
• Descriptor: N-terminal Xaa-Pro-Lys N-methyltransferase 1, (6D6)PPKRIA(NH2), DC100-1 (3 entities in total)
• Functional Keywords: methyltransferase, enzyme, inhibitor complex, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 28407.38

Authors

Noinaj, N.,Chen, D.,Huang, R. (deposition date: 2018-06-18, release date: 2019-04-03, Last modification date: 2024-11-06)

Primary citation

Chen, D.,Dong, G.,Noinaj, N.,Huang, R.
Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1.
J. Med. Chem., 62:3773-3779, 2019

PubMed Abstract: Protein N-terminal methyltransferase 1 (NTMT1) plays an important role in regulating mitosis and DNA repair. Here, we describe the discovery of a potent NTMT1 bisubstrate inhibitor 4 (IC = 35 ± 2 nM) that exhibits greater than 100-fold selectivity against a panel of methyltransferases. We also report the first crystal structure of NTMT1 in complex with an inhibitor, which revealed that 4 occupies substrate and cofactor binding sites of NTMT1.

PubMed: 30883119
DOI: 10.1021/acs.jmedchem.9b00206

Experimental method

X-RAY DIFFRACTION (1.475 Å)