Laurence H. Pearl

TL;DR: Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp 90 and not the binding to incompletely folded client polypeptides as previously suggested.

TL;DR: Present knowledge of Hsp90 structure and function gleaned from crystallographic studies of individual domains and recent progress in obtaining a structure for the ATP-bound conformation of the intact dimeric chaperone are discussed.

TL;DR: Crystal structure determinations of Hsp90 N-terminal domain complexes with geldanamycin and radicicol identify key aspects of their nucleotide mimicry and suggest a rational basis for the design of novel antichaperone drugs.

TL;DR: The structure reveals the complex architecture of the ‘closed’ state of the Hsp90 chaperone, the extensive interactions between domains and between protein chains, the detailed conformational changes in the amino-terminal domain that accompany ATP binding, and the structural basis for stabilization of the closed state by p23/Sba1.

TL;DR: 6-bromoindirubins provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3, and closely mimicked Wnt signaling in Xenopus embryos.