Study of the movement of the WPD flexible loop of human protein tyrosine phosphatase PTP1B and the factors that influence it
KATZ WISEL, Aline
(2011)
Study of the movement of the WPD flexible loop of human protein tyrosine phosphatase PTP1B and the factors that influence it.
Thèses de doctorat, Full text available as:
AbstractThis work presents the structural study of the movement of the WPD flexible loop of human enzyme PTP1B in the presence of different halogen ions. The protein of interest was co-crystallized with different concentrations of acetate buffer solution and halogens (Br- and I-), and their three-dimensional structures were determined. In the complex with the bromide ion, the WPD loop was found in both the closed and open conformation, while in the iodide complex only the closed conformation was observed. This would be indicating a relationship between the nature of the ion and the conformation of the loop. Crystallographic studies have also allowed the identification of a correlation between the concentration of the halide present in the solution in which the crystal was obtained and the conformation of the WPD loop. The collective motions of the complex were studied employing Molecular Dynamics simulations. During these simulations, the protein-bromide complex presented a conformational change, which was not observed for the protein-iodide complex. Geometry optimizations employing hybrid methods are being carried out for four systems: PTP1B-bromide complex with the loop in the closed conformation; the same complex with the open loop conformation; PTP1B-iodide complex with the loop in the closed conformation; and the same complex with the loop in the open conformation. The accurate determination of the region to be studied at a high level of theory is critical for the accurate use of hybrid methods. This work presents the methodology used to determine that region, and to identify the residues interacting with the corresponding ion. Repository Staff Only: edit this item |
