PDBsum entry 4ce3

Chaperone

PDB id: 4ce3

Contents

Protein chain

214 a.a.

Ligands

L4V

Waters ×156

PDB id:

4ce3

Name:

Chaperone

Title:

Hsp90 n-terminal domain bound to macrolactam analogues of radicicol.

Structure:

Atp-dependent molecular chaperone hsp82. Chain: a. Fragment: n-terminus, residues 1-214. Synonym: 82 kda heat shock protein, heat shock protein hsp90 heat- inducible isoform, hsp90. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.31Å R-factor: 0.198 R-free: 0.238

Authors:

S.M.Roe,S.Parry-Morris,C.Prodromou

Key ref:

B.L.Dutton et al. (2014). Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90. Org Biomol Chem, 12, 1328-1340. PubMed id: 24435512 DOI: 10.1039/c3ob42211a

Date:

08-Nov-13 Release date: 29-Jan-14

Protein chain

P02829  (HSP82_YEAST) -  ATP-dependent molecular chaperone HSP82 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 709 a.a.

Struc: 214 a.a.

DOI no: 10.1039/c3ob42211a

Org Biomol Chem 12:1328-1340 (2014)

PubMed id: 24435512

Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90.

B.L.Dutton, R.R.Kitson, S.Parry-Morris, S.M.Roe, C.Prodromou, C.J.Moody.

ABSTRACT

A series of macrolactam analogues of the naturally occurring resorcylic acid lactone radicicol have been synthesised from methyl orsellinate in 7 steps, involving chlorination, protection of the two phenolic groups, and hydrolysis to the benzoic acid. Formation of the dianion and quenching with a Weinreb amide results in acylation of the toluene methyl group that is followed by amide formation and ring closing metathesis to form the macrocyclic lactam. Final deprotection of the phenolic groups gives the desired macrolactams whose binding to the N-terminal domain of yeast Hsp90 was studied by isothermal titration calorimetry and protein X-ray crystallography.