1yts
From Proteopedia
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'''A LIGAND-INDUCED CONFORMATIONAL CHANGE IN THE YERSINIA PROTEIN TYROSINE PHOSPHATASE''' | '''A LIGAND-INDUCED CONFORMATIONAL CHANGE IN THE YERSINIA PROTEIN TYROSINE PHOSPHATASE''' | ||
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[[Category: Schubert, H L.]] | [[Category: Schubert, H L.]] | ||
[[Category: Stuckey, J A.]] | [[Category: Stuckey, J A.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:46:49 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:46, 3 May 2008
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. 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 Page seeded by OCA on Sat May 3 16:46:49 2008
