Download MendeleyStructure determination of T cell protein-tyrosine phosphatase.
Iversen, L.F., Moller, K.B., Pedersen, A.K., Peters, G.H., Petersen, A.S., Andersen, H.S., Branner, S., Mortensen, S.B., Moller, N.P.(2002) J Biol Chem 277: 19982-19990
- PubMed: 11907034
- DOI: https://doi.org/10.1074/jbc.M200567200
- Primary Citation of Related Structures:
1L8K - PubMed Abstract:
Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided. We have previously co-crystallized PTP1B with a number of low molecular weight inhibitors that inhibit TC-PTP with similar efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the same set of inhibitors. This seems to be due to a multimerization process where residues 130-132, the DDQ loop, from one molecule is inserted into the active site of the neighboring molecule, resulting in a continuous string of interacting TC-PTP molecules. Importantly, despite the high degree of functional and structural similarity between TC-PTP and PTP1B, we have been able to identify areas close to the active site that might be addressed to develop selective inhibitors of each enzyme.
Organizational Affiliation:
Protein Chemistry and Signal Transduction, Novo Nordisk, DK-2880 Bagsvaerd, Denmark. [email protected]
