8P4H
Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound IDEAYA cmpd A
Summary for 8P4H
| Entry DOI | 10.2210/pdb8p4h/pdb |
| Descriptor | S-adenosylmethionine synthase isoform type-2, 7-chloranyl-4-[(3R)-3-fluoranylpyrrolidin-1-yl]-1-phenyl-quinazolin-2-one, GLYCEROL, ... (7 entities in total) |
| Functional Keywords | methionine adenosyltransferase, sam, allosteric inhibitor, transferase, transferase-inhibitor complex |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 185814.90 |
| Authors | Thomsen, M.,Thieulin-Pardo, G.,Neumann, L. (deposition date: 2023-05-21, release date: 2023-08-30, Last modification date: 2024-10-23) |
| Primary citation | Kalliokoski, T.,Kettunen, H.,Kumpulainen, E.,Kettunen, E.,Thieulin-Pardo, G.,Neumann, L.,Thomsen, M.,Paul, R.,Malyutina, A.,Georgiadou, M. Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening. Bioorg.Med.Chem.Lett., 94:129450-129450, 2023 Cited by PubMed Abstract: Methionine adenosyltransferase 2A (MAT2A) has been indicated as a drug target for oncology indications. Clinical trials with MAT2A inhibitors are currently on-going. Here, a structure-based virtual screening campaign was performed on the commercially available chemical space which yielded two novel MAT2A-inhibitor chemical series. The binding modes of the compounds were confirmed with X-ray crystallography. Both series have acceptable physicochemical properties and show nanomolar activity in the biochemical MAT2A inhibition assay and single-digit micromolar activity in the proliferation assay (MTAP -/- cell line). The identified compounds and the relating structural data could be helpful in related drug discovery projects. PubMed: 37591318DOI: 10.1016/j.bmcl.2023.129450 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.71 Å) |
Structure validation
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