1sug

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Revision as of 17:11, 12 November 2007

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spinqualitylabelsall models 1sug, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

1.95 A structure of apo protein tyrosine phosphatase 1B

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative, regulator of insulin and leptin signalling and is therefore considered to, be an important molecular target for the treatment of type 2 diabetes and, obesity. Detailed structural information about the structure of PTP1B, including the conformation and flexibility of active-site residues as well, as the water-molecule network, is a key issue in understanding ligand, binding and enzyme kinetics and in structure-based drug design. A 1.95 A, apo PTP1B structure has been obtained, showing four highly coordinated, water molecules in the active-site pocket of the enzyme; hence, the active, site is highly solvated in the apo state. Three of the water molecules are, located at positions that approximately correspond to the positions of the, phosphate O atoms of the natural substrate phosphotyrosine and form a, similar network of hydrogen bonds. The active-site WPD-loop was found to, be in the closed conformation, in contrast to previous observations of, wild-type PTPs in the apo state, in which the WPD-loop is open. The closed, conformation is stabilized by a network of hydrogen bonds. These results, provide new insights into and understanding of the active site of PTP1B, and form a novel basis for structure-based inhibitor design.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]

About this Structure

1SUG is a Single protein structure of sequence from Homo sapiens with TRS and GOL as ligands. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.

Reference

Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B., Pedersen AK, Peters G GH, Moller KB, Iversen LF, Kastrup JS, Acta Crystallogr D Biol Crystallogr. 2004 Sep;60(Pt 9):1527-34. Epub 2004, Aug 26. PMID:15333922

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