Structural highlights
8p1w is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 1.15Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
METK2_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Publication Abstract from PubMed
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.
Discovery of novel methionine adenosyltransferase 2A (MAT2A) allosteric inhibitors by structure-based virtual screening.,Kalliokoski T, Kettunen H, Kumpulainen E, Kettunen E, Thieulin-Pardo G, Neumann L, Thomsen M, Paul R, Malyutina A, Georgiadou M Bioorg Med Chem Lett. 2023 Aug 15;94:129450. doi: 10.1016/j.bmcl.2023.129450. PMID:37591318[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2023 Aug 15;94:129450. PMID:37591318 doi:10.1016/j.bmcl.2023.129450
