Molecular recognition - from single target to protein complexes

Add to your list(s) Download to your calendar using vCal

• Dr Agata Kranjc Pietrucci from International School of Advanced Studies, Trieste, Italy
• Thursday 15 October 2009, 11:00-12:00
• Seminar Room, Sanger Building.

If you have a question about this talk, please contact Marko Hyvonen.

I will talk about structural predictions of Ca2+-binding domain in human Bestrophin­1 (hBest-1). We constructed homology models of the hBest1 Ca2+ binding domain identified the   residues binding Ca2+  and predicted the effects of their mutations. Electrophysiological experiments  confirmed our theoretical  predictions.  Then I will present the immunotherapy as possible strategy to treat prion disease. We investigated the antiprion effects of a recombinant scFv D18 (single chain variable fragment D18). We showed that binds  to a cellular prion protein (PrPC) and reduces the level of infectious, scrapie prion protein (PrPSc) in infected cells. We also determined the key residues for the molecular recognition process between the  PrPC and the scFv D18. 

I will also summarize results from the study in which we established a computational protocol to address the problem of ligands binding to proteins that lack deep binding pockets, like prion protein.

In the second part of my talk I will explain about modelling the Bcr­Abl pathway interactions to better understand drug effects. Bcr-Abl is involved in chronic myeloid leukaemia – the most common adult  leukaemia.Its molecular network has been solved. Based on these data   we   decided  to  study  the mechanism of interactions   between   Bcr-­Abl and each of its partner   proteins.   Understanding the interaction mechanism can help to identify other possible drug targets or drugable regions of the Bcr­Abl complex. Treatment for chronic myeloid leukaemia was significantly improved in last years, but despite  this the main clinical problems remain resistance and intolerance. Therefore, we will also explore the  influence of the Bcr-Abl inhibitors on protein complex assembly and consequently on the signalling  pathway. Atomistic knowledge of how drug binding remodels Bcr­Abl complex will facilitate design of new compounds overcoming some clinical limitations.

This talk is part of the Experimental and Computational Aspects of Structural Biology and Applications to Drug Discovery series.

This talk is included in these lists:

• Cambridge Infectious Diseases
• PMRFPS's
• Seminar Room, Sanger Building
• Seminars at the Department of Biochemistry
• biochem seminars
• ndk22's list
• rc781
• se393's list

Note that ex-directory lists are not shown.