PI: Akke (LU)
Project: Protein structural dynamics, interactions and
drug design
Funding ends: 31 December, 2002
Co-Supervisor: Mats Wikström
Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP), a well-characterised enzyme of 157 amino acid residues, has been shown to dimerise in phosphate buffer. The dissociation constant of the dimerisation has been determined with high accuracy by monitoring NMR chemical shifts as a function of protein concentration. The residues exhibiting concentration-dependent chemical shifts map onto one contiguous region of the three-dimensional structure, showing that the mode of dimerisation is similar to that observed in the crystal structure of the S19A mutant dimer. The dimer can be viewed as a model of a target LMW-PTP complex, as a tyrosine from one monomer is inserted into the active site of the other monomer. In order to elucidate the dynamics of both the free form LMW-PTP and the dimer, 15N-relaxation measurements have been conducted at four different LMW-PTP concentrations. Separation of the monomer and dimer contributions to the relaxation is underway.
Posters on this work were presented at the SBNet Annual Conference in Tällberg, Sweden, and at the EMBO course on Multidimensional NMR in Structural Biology in Il Ciocco, Italy.
Conferences and Symposia attended 2000
* Tällberg, SBNet Annual Conference, 912 June 2000.
* International Conference on Magnetic Resonance in
Biological Systems, Florence, Italy, 2025 Aug 2000.
* The Impact of Structural Biology in Cell Biology and
Genetics, symposium, Panum Institut, Copenhagen, 19
Oct 2000.
Courses Attended and Passed 2000
* Statistical Thermodynamics, Gothenburg University,
Oct 1999 Jan 2000.
* Structure Assisted Drug Design, The Karolinska Institute,
1316 June 2000.
* EMBO course on Multidimensional NMR in Structural
biology, Il Ciocco Conference Centre, Italy, 13-18
Aug 2000.
Latest update at 5 March, 2001.