2XD6
Hsp90 complexed with a resorcylic acid macrolactone.
Summary for 2XD6
| Entry DOI | 10.2210/pdb2xd6/pdb |
| Related | 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 |
| Descriptor | 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) |
| Functional Keywords | chaperone, inhibitor, atpase |
| Biological source | SACCHAROMYCES CEREVISIAE (BAKER'S YEAST) |
| Cellular location | Cytoplasm : P02829 |
| Total number of polymer chains | 1 |
| Total formula weight | 24943.75 |
| Authors | Roe, S.M.,Prodromou, C.,Pearl, L.H.,Moody, C.J. (deposition date: 2010-04-29, release date: 2010-08-11, Last modification date: 2023-12-20) |
| Primary citation | 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 Cited by 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: 20661961DOI: 10.1002/CHEM.201001119 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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