Dear Wenhe, One example we have is the protein kinase Nek2. We co-crystallised with ADP and then soaked in the inhibitors. The activation loop was free to move around and adopt a number of different conformations (e.g. to DFG-out conformation).
References: Westwood I, Cheary D-M, Baxter JE, Richards MW, van Montfort R, Fry AM, Bayliss R (2009) Insights into the conformational variability and regulation of human Nek2 kinase. J. Mol. Biol. 386(2):476-85 Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung K-MJ, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG, Collins I, van Monfort RLM, Aherne W, Bayliss R, Hoelder S (2010) Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization. J. Med. Chem. 53(21):7682-98. Solanki S, Innocenti P, Mas-Droux C, Boxall K, Barillari C, van Montfort RLM, Aherne GW, Bayliss R, and Hoelder S (2011) Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure−Activity Relationship. J. Med. Chem. 54: 1626-1639 Cheers Richard ============================= Dr Richard Bayliss, Reader in Structural Biology Department of Biochemistry Henry Wellcome Building University of Leicester Lancaster Road, Leicester LE1 9HN Tel: 0116 2297100 Web: http://www2.le.ac.uk/departments/biochemistry/staff/richard-bayliss/research Elite Without Being Elitist Times Higher Awards Winner 2007, 2008, 2009, 2010, 2011 Follow us on Twitter http://twitter.com/uniofleicester On 9 Oct 2012, at 14:33, WENHE ZHONG wrote: Dear CCP4 members, Recently, I got a ligand soaking structure to clearly show a large domain (~100 amino acids) movement compared to the no soaking structure. Although there are some reported examples of this enzyme to suggest the flexibility of this large domain which is relevant to substrate binding. But it is the first time I can see it happen in crystal soaking procedure. In this case, I am pleased by this result. My question is, do you have any other example like mine, where domain (or loop) movement is observed in crystal during ligand soaking procedure? It would be very helpful for me to relate my result to other similar examples. Thank you very much. King regards, Wenhe
