4NVQ

Human G9a in Complex with Inhibitor A-366

Summary for 4NVQ

• Entry DOI: 10.2210/pdb4nvq/pdb
• Descriptor: Histone-lysine N-methyltransferase EHMT2, 5'-methoxy-6'-[3-(pyrrolidin-1-yl)propoxy]spiro[cyclobutane-1,3'-indol]-2'-amine, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: lysine methyl transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q96KQ7
• Total number of polymer chains: 2
• Total formula weight: 67699.51

Authors

Sweis, R.F.,Pliushchev, M.,Brown, P.J.,Guo, J.,Li, F.,Maag, D.,Petros, A.M.,Soni, N.B.,Tse, C.,Vedadi, M.,Michaelides, M.R.,Chiang, G.G.,Pappano, W.N. (deposition date: 2013-12-05, release date: 2014-01-15, Last modification date: 2024-02-28)

Primary citation

Sweis, R.F.,Pliushchev, M.,Brown, P.J.,Guo, J.,Li, F.,Maag, D.,Petros, A.M.,Soni, N.B.,Tse, C.,Vedadi, M.,Michaelides, M.R.,Chiang, G.G.,Pappano, W.N.
Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.
ACS Med Chem Lett, 5:205-209, 2014

PubMed Abstract: G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.

PubMed: 24900801
DOI: 10.1021/ml400496h

Experimental method

X-RAY DIFFRACTION (2.03 Å)