4EGK

Human Hsp90-alpha ATPase domain bound to Radicicol

Summary for 4EGK

• Entry DOI: 10.2210/pdb4egk/pdb
• Related: 4EGH 4EGI
• Descriptor: Heat shock protein HSP 90-alpha, RADICICOL (3 entities in total)
• Functional Keywords: bergerat fold, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 26435.02

Authors

Chen, W.J.,Wood, S.P. (deposition date: 2012-03-31, release date: 2012-05-23, Last modification date: 2024-02-28)

Primary citation

Austin, C.,Pettit, S.N.,Magnolo, S.K.,Sanvoisin, J.,Chen, W.,Wood, S.P.,Freeman, L.D.,Pengelly, R.J.,Hughes, D.E.
Fragment screening using capillary electrophoresis (CEfrag) for hit identification of heat shock protein 90 ATPase inhibitors.
J Biomol Screen, 17:868-876, 2012

PubMed Abstract: CEfrag is a new fragment screening technology based on affinity capillary electrophoresis (ACE). Here we report on the development of a mobility shift competition assay using full-length human heat shock protein 90α (Hsp90α), radicicol as the competitor probe ligand, and successful screening of the Selcia fragment library. The CEfrag assay was able to detect weaker affinity (IC(50) >500 µM) fragments than were detected by a fluorescence polarization competition assay using FITC-labeled geldanamycin. The binding site of selected fragments was determined by co-crystallization with recombinant Hsp90α N-terminal domain and X-ray analysis. The results of this study confirm that CEfrag is a sensitive microscale technique enabling detection of fragments binding to the biological target in near-physiological solution.

PubMed: 22573733
DOI: 10.1177/1087057112445785
PDB entries with the same primary citation

Experimental method

X-RAY DIFFRACTION (1.69 Å)