Co-crystal structure of the HSP90 ATP binding domain in complex with 4-(2,4-dichloro-5-methoxyphenyl)-6-methylpyrimidin-2-amine
[HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. 
Publication Abstract from PubMed
A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (K(d)=1.3nM, K(i)=15nM, and cellular IC(50)=0.5muM).
Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone.,Kung PP, Sinnema PJ, Richardson P, Hickey MJ, Gajiwala KS, Wang F, Huang B, McClellan G, Wang J, Maegley K, Bergqvist S, Mehta PP, Kania R Bioorg Med Chem Lett. 2011 Jun 15;21(12):3557-62. Epub 2011 May 5. PMID:21612924
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.