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Publication Abstract from PubMed

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.

Structure determination of T cell protein-tyrosine phosphatase.,Iversen LF, Moller KB, Pedersen AK, Peters GH, Petersen AS, Andersen HS, Branner S, Mortensen SB, Moller NP J Biol Chem. 2002 May 31;277(22):19982-90. Epub 2002 Mar 20. PMID:11907034^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.