4AI8

FACTOR INHIBITING HIF-1 ALPHA IN COMPLEX WITH DAMINOZIDE

4AI8 の概要

• エントリーDOI: 10.2210/pdb4ai8/pdb
• 関連するPDBエントリー: 1H2K 1H2L 1H2M 1H2N 1IZ3 1MZE 1MZF 1YCI 2CGN 2CGO 2W0X 2WA3 2WA4 2XUM 2Y0I 2YC0 2YDE
• 分子名称: HYPOXIA-INDUCIBLE FACTOR 1-ALPHA INHIBITOR, SULFATE ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, dioxygenase, metal-binding, helix-loop-helix-beta, dsbh, facial triad, transcription and epigenetic regulation, ankyrin repeat domain, beta-hydroxylation, transcription activator/inhibitor
• 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: 41592.73

構造登録者

King, O.N.F.,Chowdhury, R.,Rose, N.R.,McDonough, M.A.,Clifton, I.J.,Schofield, C.J.,Kawamura, A. (登録日: 2012-02-08, 公開日: 2012-10-03, 最終更新日: 2023-12-20)

主引用文献

Rose, N.R.,Woon, E.C.,Tumber, A.,Walport, L.J.,Chowdhury, R.,Li, X.S.,King, O.N.,Lejeune, C.,Ng, S.S.,Krojer, T.,Chan, M.C.,Rydzik, A.M.,Hopkinson, R.J.,Che, K.H.,Daniel, M.,Strain-Damerell, C.,Gileadi, C.,Kochan, G.,Leung, I.K.,Dunford, J.,Yeoh, K.K.,Ratcliffe, P.J.,Burgess-Brown, N.,von Delft, F.,Muller, S.,Marsden, B.,Brennan, P.E.,McDonough, M.A.,Oppermann, U.,Klose, R.J.,Schofield, C.J.,Kawamura, A.
Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.
J. Med. Chem., 55:6639-6643, 2012

PubMed Abstract: The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups.

PubMed: 22724510
DOI: 10.1021/jm300677j

実験手法

X-RAY DIFFRACTION (2.4 Å)