000008778 001__ 8778
000008778 005__ 20130211173032.0
000008778 0248_ $$aoai:doc.rero.ch:20080219130927-HH$$pthesis$$zcdu34$$zthesis_urn$$zunige$$zreport$$zbook$$zjournal$$zcdu16$$zpostprint$$zpreprint$$zcdu1$$zdissertation$$zcdu615
000008778 035__ $$aR004613027
000008778 041__ $$aeng
000008778 080__ $$a615
000008778 100__ $$aMoretti, Loris
000008778 245__ $$9eng$$aExploring structure and plasticity of tyrosine kinase domains for drug discovery
000008778 300__ $$a168 p.
000008778 500__ $$aCotutelle: Università degli studi di Padova; Department of Pharmaceutical Sciences
000008778 502__ $$92007-10-16$$aThèse de doctorat : Université de Genève, 2007 ; Sc. 3904
000008778 506__ $$ffree
000008778 520__ $$9eng$$aProtein tyrosine kinases (TKs) play a crucial role in human physiology and their abnormal function, due to protein modifications, is correlated with several diseases. The clear need to understand the mechanisms and to antagonize the activities of aberrant catalytic domains of TKs (KD) fired up this thesis. Through the chapters, evaluations about sequence, structure, dynamics and ligand binding of the proteins are made using several computational tools. Firstly, the essential structural elements for molecules to bind at the ATP-binding site are defined. Then, the dynamical behavior of different KDs is classified based on the rearrangement of 5 clusters of residues. In particular, a pool of residues, found at the interface of two lobes, appears to be important for the protein conformation and motion. Finally, the investigation about the activation mechanism of oncogenic Flt3 is reported and a secondary structure element suggested as the first driving force for conformational changes.
000008778 695__ $$9eng$$atyrosine kinase ; molecular modeling ; Flt3 ; drug discovery ; structural studies
000008778 700__ $$aScappozza, Leonardo$$eDir.
000008778 700__ $$aMoro, Stefano$$eCodir.
000008778 8564_ $$fthese-MorettiL.pdf$$qapplication/pdf$$s8462993$$uhttp://doc.rero.ch/record/8778/files/these-MorettiL.pdf$$yorder:1$$zTexte intégral
000008778 918__ $$aFaculté des sciences$$bUniversité de Genève, Rue Général Dufour 24, 1211 Genève 4$$cSection des Sciences Pharmaceutiques
000008778 919__ $$aUniversité de Genève$$bGenève$$ddoc.support@rero.ch
000008778 980__ $$aTHESIS$$bUNIGE$$fTH_PHD
000008778 990__ $$a20080219130927-HH