6NT2
type 1 PRMT in complex with the inhibitor GSK3368715
Summary for 6NT2
| Entry DOI | 10.2210/pdb6nt2/pdb |
| Descriptor | Protein arginine N-methyltransferase 1, S-ADENOSYL-L-HOMOCYSTEINE, N~1~-({5-[4,4-bis(ethoxymethyl)cyclohexyl]-1H-pyrazol-4-yl}methyl)-N~1~,N~2~-dimethylethane-1,2-diamine, ... (6 entities in total) |
| Functional Keywords | inhibitor, cmplex, methyl transferase, arginine, antitumor protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 175322.42 |
| Authors | Concha, N.O. (deposition date: 2019-01-28, release date: 2019-07-10, Last modification date: 2024-11-06) |
| Primary citation | Fedoriw, A.,Rajapurkar, S.R.,O'Brien, S.,Gerhart, S.V.,Mitchell, L.H.,Adams, N.D.,Rioux, N.,Lingaraj, T.,Ribich, S.A.,Pappalardi, M.B.,Shah, N.,Laraio, J.,Liu, Y.,Butticello, M.,Carpenter, C.L.,Creasy, C.,Korenchuk, S.,McCabe, M.T.,McHugh, C.F.,Nagarajan, R.,Wagner, C.,Zappacosta, F.,Annan, R.,Concha, N.O.,Thomas, R.A.,Hart, T.K.,Smith, J.J.,Copeland, R.A.,Moyer, M.P.,Campbell, J.,Stickland, K.,Mills, J.,Jacques-O'Hagan, S.,Allain, C.,Johnston, D.,Raimondi, A.,Porter Scott, M.,Waters, N.,Swinger, K.,Boriack-Sjodin, A.,Riera, T.,Shapiro, G.,Chesworth, R.,Prinjha, R.K.,Kruger, R.G.,Barbash, O.,Mohammad, H.P. Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss. Cancer Cell, 36:100-, 2019 Cited by PubMed Abstract: Type I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginines on proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting inhibition of type I PRMTs may offer a therapeutic approach for oncology. The current report describes GSK3368715 (EPZ019997), a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models. Inhibition of PRMT5, the predominant type II PRMT, produces synergistic cancer cell growth inhibition when combined with GSK3368715. Interestingly, deletion of the methylthioadenosine phosphorylase gene (MTAP) results in accumulation of the metabolite 2-methylthioadenosine, an endogenous inhibitor of PRMT5, and correlates with sensitivity to GSK3368715 in cell lines. These data provide rationale to explore MTAP status as a biomarker strategy for patient selection. PubMed: 31257072DOI: 10.1016/j.ccell.2019.05.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.48 Å) |
Structure validation
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