2BZ5

Structure-based Discovery of a New Class of Hsp90 Inhibitors

PDB DOI: https://doi.org/10.2210/pdb2BZ5/pdb

Classification: CHAPERONE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2005-08-11 Released: 2005-10-12
Deposition Author(s): Barril, X., Brough, P., Drysdale, M., Hubbard, R.E., Massey, A., Surgenor, A., Wright, L.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.254
R-Value Work: 0.195
R-Value Observed: 0.198

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Structure-Based Discovery of a New Class of Hsp90 Inhibitors.

Barril, X., Brough, P., Drysdale, M., Hubbard, R.E., Massey, A., Surgenor, A., Wright, L.

(2005) Bioorg Med Chem Lett 15: 5187

PubMed: 16202589 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2005.08.092
Primary Citation of Related Structures:
2BZ5

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.

Organizational Affiliation

Vernalis (R&D) Ltd, Granta Park, Abington, Cambridge CB1 6GB, UK. x.barril@vernalis.com

Macromolecule Content

Total Structure Weight: 53.86 kDa
Atom Count: 3,871
Modelled Residue Count: 420
Deposited Residue Count: 470
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
HEAT SHOCK PROTEIN HSP90-ALPHA	A, B	235	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P07900 (Homo sapiens) Explore P07900 Go to UniProtKB: P07900
PHAROS: P07900 GTEx: ENSG00000080824
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P07900
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
AB4 Query on AB4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth B]	C [auth A], D [auth B]	2,5-DICHLORO-N-[4-HYDROXY-3-(2-HYDROXY-1-NAPHTHYL)PHENYL]BENZENESULFONAMIDE C₂₂ H₁₅ Cl₂ N O₄ S KDKVLAFZMJRTEA-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
AB4	BindingDB: 2BZ5	IC50: min: 700, max: 2.00e+4 (nM) from 2 assay(s)
AB4	PDBBind: 2BZ5	IC50: 700 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.254
R-Value Work: 0.195
R-Value Observed: 0.198
Space Group: P 2₁ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 64.46	α = 90
b = 88.562	β = 90
c = 98.96	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
d*TREK	data reduction
d*TREK	data scaling
AMoRE	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2005-10-12

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2005-10-12
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2018-01-31
Changes: Source and taxonomy
Version 1.4: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description