PDBsum entry 3inx

Chaperone

PDB id

3inx

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Contents

			Protein chain

					207 a.a. *

			Ligands

					DMS ×2


					JZC

			Waters ×328

* Residue conservation analysis

PDB id:

3inx

Links

Name:

Chaperone

Title:

Hsp90 n-terminal domain with pochoxime b

Structure:

Heat shock protein hsp 90-alpha. Chain: a. Fragment: unp residues 10-236, n-terminal domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hsp90aa1, hsp90a, hspc1, hspca. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.75Å

R-factor:

0.170

R-free:

0.217

Authors:

I.P.Korndoerfer

Key ref:

S.Barluenga et al. (2009). Inhibition of HSP90 with pochoximes: SAR and structure-based insights. Chembiochem, 10, 2753-2759. PubMed id: 19856365

Date:

13-Aug-09

Release date:

18-Aug-10

PROCHECK

	Headers

	References

Protein chain

P07900 (HS90A_HUMAN) - Heat shock protein HSP 90-alpha from Homo sapiens

Seq: Struc:

Seq: Struc:					732 a.a. 207 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.6.4.10 - non-chaperonin molecular chaperone ATPase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

ATP + H2O = ADP + phosphate + H⁺

ATP	+	H2O	=	ADP	+	phosphate	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

	Chembiochem 10:2753-2759 (2009)
PubMed id: 19856365

Inhibition of HSP90 with pochoximes: SAR and structure-based insights.
S.Barluenga, J.G.Fontaine, C.Wang, K.Aouadi, R.Chen, K.Beebe, L.Neckers, N.Winssinger.

ABSTRACT

The pochoximes, based on the radicicol pharmacophore, are potent inhibitors of heat shock protein 90 (HSP90) that retain their activity in vivo. Herein we report an extended library that broadly explores the structure-activity relationship (SAR) of the pochoximes with four points of diversity. Several modifications were identified that afford improved cellular efficacy, new opportunities for conjugation, and further diversifications. Cocrystal structures of pochoximes A and B with HSP90 show that pochoximes bind to a different conformation of HSP90 than radicicol and provide a rationale for the enhanced affinity of the pochoximes relative to radicicol and the pochonins.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20981667

C.Rink, F.Sasse, A.Zubrienė, D.Matulis, and M.E.Maier (2010).
Probing the influence of an allylic methyl group in zearalenone analogues on binding to Hsp90.

Chemistry, 16, 14469-14478.

21209834

I.Grad, C.R.Cederroth, J.Walicki, C.Grey, S.Barluenga, N.Winssinger, B.De Massy, S.Nef, and D.Picard (2010).
The molecular chaperone Hsp90α is required for meiotic progression of spermatocytes beyond pachytene in the mouse.

PLoS One, 5, e15770.

20661961

J.E.Day, S.Y.Sharp, M.G.Rowlands, W.Aherne, W.Lewis, S.M.Roe, C.Prodromou, L.H.Pearl, P.Workman, and C.J.Moody (2010).
Inhibition of Hsp90 with resorcylic acid macrolactones: synthesis and binding studies.

Chemistry, 16, 10366-10372.

PDB code:

2xd6

20572190

J.Garcia, S.Barluenga, K.Beebe, L.Neckers, and N.Winssinger (2010).
Concise modular asymmetric synthesis of deguelin, tephrosin and investigation into their mode of action.

Chemistry, 16, 9767-9771.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.