1yts

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spinqualitylabelsall models 1yts, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

A LIGAND-INDUCED CONFORMATIONAL CHANGE IN THE YERSINIA PROTEIN TYROSINE PHOSPHATASE

Overview

Protein tyrosine phosphatases (PTPases) play critical roles in the, intracellular signal transduction pathways that regulate cell, transformation, growth, and proliferation. The structures of several, different PTPases have revealed a conserved active site architecture in, which a phosphate-binding loop, together with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate and poise it for, nucleophilic attack by an invariant cysteine nucleophile. We previously, reported that binding of tungstate to the Yop51 PTPase from Yersinia, induced a loop conformational change that moved aspartic acid 356 into the, active site, where it can function as a general acid. This is consistent, with the aspartic acid donating a proton to the tyrosyl leaving group, during the initial hydrolysis step. In this report, using a similar, structure of the inactive Cys 403-->Ser mutant of the Yersinia PTPase, complexed with sulfate, we detail the structural and functional details of, this conformational change. In response to oxyanion binding, small, perturbations occur in active site residues, especially Arg 409, and, trigger the loop to close. Interestingly, the peptide bond following Asp, 356 has flipped to ligate a buried, active site water molecule that also, hydrogen bonds to the bound sulfate anion and two invariant glutamines., Loop closure also significantly decreases the solvent accessibility of the, bound oxyanion and could effectively shield catalytic intermediates from, phosphate acceptors other than water. We speculate that the intrinsic loop, flexibility of different PTPases may be related to their catalytic rate, and may play a role in the wide range of activities observed within this, enzyme family.

About this Structure

1YTS is a Single protein structure of sequence from Yersinia enterocolitica with SO4 as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.

Reference

A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase., Schubert HL, Fauman EB, Stuckey JA, Dixon JE, Saper MA, Protein Sci. 1995 Sep;4(9):1904-13. PMID:8528087

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