1L8K

T Cell Protein-Tyrosine Phosphatase Structure

Summary for 1L8K

• Entry DOI: 10.2210/pdb1l8k/pdb
• Descriptor: T-cell protein-tyrosine phosphatase (2 entities in total)
• Functional Keywords: protein tyrosine phosphatase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P17706
• Total number of polymer chains: 1
• Total formula weight: 36658.57

Authors

Iversen, L.F. (deposition date: 2002-03-21, release date: 2002-05-08, Last modification date: 2024-02-14)

Primary citation

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.
Structure determination of T cell protein-tyrosine phosphatase.
J.Biol.Chem., 277:19982-19990, 2002

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.

PubMed: 11907034
DOI: 10.1074/jbc.M200567200

Experimental method

X-RAY DIFFRACTION (2.56 Å)