1l8k
From Proteopedia
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'''T Cell Protein-Tyrosine Phosphatase Structure''' | '''T Cell Protein-Tyrosine Phosphatase Structure''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Iversen, L F.]] | [[Category: Iversen, L F.]] | ||
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Revision as of 20:40, 2 May 2008
T Cell Protein-Tyrosine Phosphatase Structure
Overview
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.
About this Structure
1L8K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 23:39:59 2008
