PDBsum entry 2vwc

Chaperone

PDB id

2vwc

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Contents

			Protein chain

					214 a.a. *

			Ligands

					BC2


					GOL

			Waters ×119

* Residue conservation analysis

PDB id:

2vwc

Links

Name:

Chaperone

Title:

Structure of the hsp90 inhibitor macbecin bound to the n-terminus of yeast hsp90.

Structure:

Atp-dependent molecular chaperone hsp82. Chain: a. Fragment: n-terminal domain, residues 1-219. Synonym: heat shock protein hsp90 heat-inducible isoform, 82 kda heat shock protein. Engineered: yes

Source:

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

Resolution:

2.40Å

R-factor:

0.198

R-free:

0.262

Authors:

S.M.Roe,C.Prodromou,L.H.Pearl

Key ref:

C.J.Martin et al. (2008). Molecular characterization of macbecin as an Hsp90 inhibitor. J Med Chem, 51, 2853-2857. PubMed id: 18357975

Date:

20-Jun-08

Release date:

01-Jul-08

Supersedes:

2vls

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:

Seq: Struc:					709 a.a. 214 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

	J Med Chem 51:2853-2857 (2008)
PubMed id: 18357975

Molecular characterization of macbecin as an Hsp90 inhibitor.
C.J.Martin, S.Gaisser, I.R.Challis, I.Carletti, B.Wilkinson, M.Gregory, C.Prodromou, S.M.Roe, L.H.Pearl, S.M.Boyd, M.Q.Zhang.

ABSTRACT

Macbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC50 = 2 microM) and binding with higher affinity (Kd = 0.24 microM). Structural studies reveal significant differences in their Hsp90 binding characteristics, and macbecin-induced tumor cell growth inhibition is accompanied by characteristic degradation of Hsp90 client proteins. Macbecin significantly reduced tumor growth rates (minimum T/C: 32%) in a DU145 murine xenograft. Macbecin thus represents an attractive lead for further optimization.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20937817

L.Vozzolo, B.Loh, P.J.Gane, M.Tribak, L.Zhou, I.Anderson, E.Nyakatura, R.G.Jenner, D.Selwood, and A.Fassati (2010).
Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein.

J Biol Chem, 285, 39314-39328.

19200020

M.W.Amolins, and B.S.Blagg (2009).
Natural product inhibitors of Hsp90: potential leads for drug discovery.

Mini Rev Med Chem, 9, 140-152.

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.