PDBsum entry 5aqz

Chaperone

PDB id: 5aqz

Contents

Protein chain

390 a.a.

Ligands

SGV

EDO ×4

Waters ×432

References listed in PDB file

Key reference

• Title: Exploiting protein conformational change to optimize adenosine-Derived inhibitors of hsp70.
• Authors: M.D.Cheeseman, I.M.Westwood, O.Barbeau, M.Rowlands, S.Dobson, A.M.Jones, F.Jeganathan, R.Burke, N.Kadi, P.Workman, I.Collins, R.L.Van montfort, K.Jones.
• Ref.: J Med Chem, 2016, 59, 4625-4636. [DOI no: 10.1021/acs.jmedchem.5b02001]
• PubMed id: 27119979

Abstract

HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.