2BZ5

Structure-based Discovery of a New Class of Hsp90 Inhibitors

Summary for 2BZ5

• Entry DOI: 10.2210/pdb2bz5/pdb
• Related: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM 2BT0 2BYH 2BYI
• Descriptor: HEAT SHOCK PROTEIN HSP90-ALPHA, 2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE (3 entities in total)
• Functional Keywords: atp-binding, chaperone, heat shock, nucleotide-binding, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : P07900
• Total number of polymer chains: 2
• Total formula weight: 53861.82

Authors

Barril, X.,Brough, P.,Drysdale, M.,Hubbard, R.E.,Massey, A.,Surgenor, A.,Wright, L. (deposition date: 2005-08-11, release date: 2005-10-12, Last modification date: 2025-10-01)

Primary citation

Barril, X.,Brough, P.,Drysdale, M.,Hubbard, R.E.,Massey, A.,Surgenor, A.,Wright, L.
Structure-Based Discovery of a New Class of Hsp90 Inhibitors.
Bioorg.Med.Chem.Lett., 15:5187-, 2005

PubMed Abstract: Docking-based virtual screening identified 1-(2-phenol)-2-naphthol compounds as a new class of Hsp90 inhibitors of low to sub-micromolar potency. Here we report the binding affinities and cellular activities of several members of this class. A high resolution crystal structure of the most potent compound reveals its binding mode in the ATP binding site of Hsp90, providing a rationale for the observed activity of the series and suggesting strategies for developing compounds with improved properties.

PubMed: 16202589
DOI: 10.1016/J.BMCL.2005.08.092

Experimental method

X-RAY DIFFRACTION (1.9 Å)