Tomas Åkerud
PI: Akke (LU)
Project: Protein structural dynamics, interactions and drug design
Funding ends: 31 December, 2002
Co-Supervisor: Mats Wikström
Research activities
The study of the phosphate loaded state of Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP, see Research Report 2000) has been concluded. The relaxation contributions of the monomer and dimer have been separated and model-free analyses of the monomer and dimer have been conducted. Relaxation data of satisfactory precision were extracted for the monomer, enabling model-free analyses of backbone fluctuations on pico- to nanosecond time scales. The relaxation data for the dimer are of lower quality, but show that the rotational diffusion tensor of the dimer is highly anisotropic, and its orientation in the molecular frame is in agreement with that expected from the crystal structure and hydrodynamic calculations. Qualitative information on monomer-dimer exchange and intramolecular conformational exchange was obtained from the concentration dependence of auto- and cross-correlated relaxation rates. The loop containing the catalytically important Asp 129 fluctuates between different conformations in both the monomeric and dimeric (target bound) states. The exchange rate compares rather well with those of the chemical steps of the catalysed reaction, supporting the existing hypothesis that catalysis and enzyme dynamics may be coupled. The side chain of Trp 49, which is important for substrate specificity, exhibits conformational dynamics in the monomer that are largely quenched upon formation of the dimer, suggesting that binding is associated with the selection of a single side chain conformer.
The results from this study have been compiled ("Intramolecular dynamics of low molecular weight protein tyrosine phosphatase in monomer-dimer equilibrium studied by NMR. A model for changes in dynamics upon target binding") and publicly defended for a licentiate degree in Physical Chemistry at the Department of Biophysical Chemistry, Lund University, 19 Dec 2001. A talk and poster on LMW-PTP was presented at the SBNet Annual Conference in Tällberg, Sweden.
Conferences
Tällberg, SBNet Annual Conference, 15-18 June 2001
Teaching
* Thermodynamics practical, The Joule-Thomson effect, 19-29 March 2001
* Quantum mechanics practical, IR-spectroscopy, 1-15 Oct 2001
* Biophysical chemistry practical, Protein Sequence and Structure, Databases and Molecular Graphics, 30 Oct 2001
* Biophysical chemistry practical, Ramachandran diagram, 6 Nov 2001
Courses attended and passed
Writing Science, Karolinska Institute, 19-22 Feb 2001
Latest update at 29 March, 2001.