8P1V

Crystal structure of human methionine adenosyltransferase 2A (MAT2A) in complex with SAM and allosteric compound 2

これはPDB形式変換不可エントリーです。

8P1V の概要

• エントリーDOI: 10.2210/pdb8p1v/pdb
• 分子名称: S-adenosylmethionine synthase isoform type-2, S-ADENOSYLMETHIONINE, 6-cyclopropyl-~{N}-(2-methylindazol-5-yl)-1-propan-2-yl-pyrazolo[3,4-b]pyridine-4-carboxamide, ... (6 entities in total)
• 機能のキーワード: methionine adenosyltransferase, s-adenosylmethionine synthase isoform 2 type-2, sam, allosteric inhibitor, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46866.64

構造登録者

Thomsen, M.,Thieulin-Pardo, G.,Neumann, L. (登録日: 2023-05-12, 公開日: 2023-08-30)

主引用文献

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

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: 37591318
DOI: 10.1016/j.bmcl.2023.129450

実験手法

X-RAY DIFFRACTION (1.54 Å)