4FMU

Crystal structure of Methyltransferase domain of human SET domain-containing protein 2 Compound: Pr-SNF

4FMU の概要

• エントリーDOI: 10.2210/pdb4fmu/pdb
• 分子名称: Histone-lysine N-methyltransferase SETD2, ZINC ION, (2S,5S)-2-amino-6-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]-5-(propylamino)hexanoic acid, ... (5 entities in total)
• 機能のキーワード: structural genomics consortium, sgc, methyltransferase, set domain-containing protein 2, pr-snf, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Probable): Q9BYW2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32575.18

構造登録者

Dong, A.,Zeng, H.,Ibanez, G.,Zheng, W.,Tempel, W.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Brown, P.J.,Min, J.,Luo, M.,Wu, H.,Structural Genomics Consortium (SGC) (登録日: 2012-06-18, 公開日: 2012-09-05, 最終更新日: 2023-09-13)

主引用文献

Zheng, W.,Ibanez, G.,Wu, H.,Blum, G.,Zeng, H.,Dong, A.,Li, F.,Hajian, T.,Allali-Hassani, A.,Amaya, M.F.,Siarheyeva, A.,Yu, W.,Brown, P.J.,Schapira, M.,Vedadi, M.,Min, J.,Luo, M.
Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2.
J.Am.Chem.Soc., 134:18004-18014, 2012

PubMed Abstract: Epigenetic regulation is involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogation of the functions of individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given the emerging need for such small molecules, we envisioned an approach to identify target-specific methyltransferase inhibitors by screening privileged small-molecule scaffolds against diverse methyltransferases. In this work, we demonstrated the feasibility of such an approach by identifying the inhibitors of SETD2. N-propyl sinefungin (Pr-SNF) was shown to interact preferentially with SETD2 by matching the distinct transition-state features of SETD2's catalytically active conformer. With Pr-SNF as a structure probe, we further revealed the dual roles of SETD2's post-SET loop in regulating substrate access through a distinct topological reconfiguration. Privileged sinefungin scaffolds are expected to have broad use as structure and chemical probes of methyltransferases.

PubMed: 23043551
DOI: 10.1021/ja307060p

実験手法

X-RAY DIFFRACTION (2.1 Å)