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Doctoral thesis
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Understanding tyrosine kinase domain plasticity through identification of protein residues involved in the control of the conformational transition

ContributorsBoubeva, Ralitza
Defense date2011-03-30
Abstract

The aim of this thesis consisted in the identification of key amino acids residues governing the transition from active to inactive protein kinase domain conformation. We used the kinase domain of c-Src as a case study because of the wealth of structural information on this protein. We could demonstrate that residues governing the kinase domain dynamics of c-Src are located far from the ATP-binding site and form a network of hydrophobic interactions at the interface between the N-lobe and the C-lobe of the kinase domain. The identified amino acids and in particular Leu317 dictate the conformational plasticity of the kinase domain by influencing the rate of the DFG-flip. Furthermore, we could provide experimental evidence that the DFG-flip is the most probable molecular mechanism for the release of ADP at the end of the catalytic cycle and that both DFG-in and DFG-out conformations are present within the catalytic cycle of c-Src.

eng
Keywords
  • Tyrosine kinase
  • Conformational plasticity
  • C-Src
  • DFG-flip
Citation (ISO format)
BOUBEVA, Ralitza. Understanding tyrosine kinase domain plasticity through identification of protein residues involved in the control of the conformational transition. 2011. doi: 10.13097/archive-ouverte/unige:17314
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Technical informations

Creation10/19/2011 11:36:00 AM
First validation10/19/2011 11:36:00 AM
Update time03/14/2023 5:03:48 PM
Status update03/14/2023 5:03:48 PM
Last indexation01/29/2024 7:16:07 PM
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