Hi Xiaopeng, There is no sign of extra density anywhere? Could the inhibitors be binding at a site other than the active site? Is the active site accessible from the solvent channels in the crystal?
If not, best thing I can suggest is to try and co-crystallise protein with inhibitor - mix the two together prior to screening. There is a nice review about obtaining protein:ligand complexes here: http://scripts.iucr.org/cgi-bin/paper?ba5097 Good luck! David ============================ David C. Briggs PhD Father, Structural Biologist and Sceptic ============================ University of Manchester E-mail: david.c.bri...@manchester.ac.uk ============================ http://manchester.academia.edu/DavidBriggs (v.sensible) http://xtaldave.wordpress.com/ (sensible) http://xtaldave.posterous.com/ (less sensible) Twitter: @xtaldave Skype: DocDCB ============================ 2010/8/28 胡小鹏 <huxp...@mail.sysu.edu.cn>: > Dear all, > We are working on protein-inhibitor complex crystal structures, although > we did get nice crystals and soaked them with inhibitor for several days, all > structures we obtained were empty!!There are nothing at the active site. For > several crystals. their color turned very clearly from colorless to yellow > the color of the inhibitors, nothing found either. > These inhibitors work very well in enzyme assay. We, especially our > students, are very depressed... > Any suggestions will be really appreciated! > > > > > Xiaopeng Hu, D.Sc., > School of Pharmaceutical Sciences > Sun Yat-sen University, > Higher Education Mega Center > Guangzhou, Guangdong, China 510006 > Tel. +86 020 39943032 >
