title: Conformational motions regulate phosphoryl transfer in related protein tyrosine phosphatases.
abstract: Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.
authors: Sean K
authors: SK
authors: Whittier
authors: Alvan C
authors: AC
authors: Hengge
authors: J Patrick
authors: JP
authors: Loria
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D002384:Catalysis; D020134:Catalytic Domain; D006801:Humans; D009038:Motion; D019906:Nuclear Magnetic Resonance, Biomolecular; D010710:Phosphates / Q000737:chemistry*; D011487:Protein Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000737:chemistry*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D014638:Vanadates / Q000737:chemistry
chemical_list: D001425:Bacterial Outer Membrane Proteins; D010710:Phosphates; D014638:Vanadates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia
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