2xd6
From Proteopedia
Contents |
Hsp90 complexed with a resorcylic acid macrolactone.
Template:ABSTRACT PUBMED 20661961
Function
[HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. 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. Required for growth at high temperatures.[1]
About this Structure
2xd6 is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
See Also
Reference
- Day JE, Sharp SY, Rowlands MG, Aherne W, Lewis W, Roe SM, Prodromou C, Pearl LH, Workman P, Moody CJ. Inhibition of Hsp90 with Resorcylic Acid Macrolactones: Synthesis and Binding Studies. Chemistry. 2010 Jul 26. PMID:20661961 doi:10.1002/chem.201001119
- ↑ Proisy N, Sharp SY, Boxall K, Connelly S, Roe SM, Prodromou C, Slawin AM, Pearl LH, Workman P, Moody CJ. Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol. Chem Biol. 2006 Nov;13(11):1203-15. PMID:17114002 doi:10.1016/j.chembiol.2006.09.015
