2XD6

Hsp90 complexed with a resorcylic acid macrolactone.

2XD6 の概要

• エントリーDOI: 10.2210/pdb2xd6/pdb
• 関連するPDBエントリー: 1A4H 1AH6 1AH8 1AM1 1AMW 1BGQ 1HK7 1US7 1USU 1USV 1ZW9 1ZWH 2AKP 2BRC 2BRE 2CG9 2CGE 2CGF 2IWS 2IWU 2IWX 2VLS 2VW5 2VWC 2WEP 2WEQ 2WER
• 分子名称: ATP-DEPENDENT MOLECULAR CHAPERONE HSP82, (5Z)-13-CHLORO-14,16-DIHYDROXY-1,11-DIOXO-3,4,7,8,9,10,11,12-OCTAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-6-CARBALDEHYDE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: chaperone, inhibitor, atpase
• 由来する生物種: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• 細胞内の位置: Cytoplasm : P02829
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24943.75

構造登録者

Roe, S.M.,Prodromou, C.,Pearl, L.H.,Moody, C.J. (登録日: 2010-04-29, 公開日: 2010-08-11, 最終更新日: 2023-12-20)

主引用文献

Day, J.E.H.,Sharp, S.Y.,Rowlands, M.G.,Aherne, W.,Lewis, W.,Roe, S.M.,Prodromou, C.,Pearl, L.H.,Workman, P.,Moody, C.J.
Inhibition of Hsp90 with Resorcylic Acid Macrolactones. Synthesis and Binding Studies.
Chemistry, 16:10366-, 2010

PubMed Abstract: A series of resorcylic acid macrolactones, analogues of the natural product radicicol has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. The synthesis involves acylation of an ortho-toluic acid dianion, esterification, followed by a ring-closing metathesis to form the macrocycle. Subsequent manipulation of the protected hydroxymethyl side chain allows access to a range of new analogues following deprotection of the two phenolic groups. Co-crystallization of one of the new macrolactones with the N-terminal domain of yeast Hsp90 confirms that it binds in a similar way to the natural product radicicol and to our previous synthetic analogues, but that the introduction of the additional hydroxymethyl substituent appears to result in an unexpected change in conformation of the macrocyclic ring. As a result of this conformational change, the compounds bound less favorably to Hsp90.

PubMed: 20661961
DOI: 10.1002/CHEM.201001119

実験手法

X-RAY DIFFRACTION (2.2 Å)