Conformational Motions Regulate Phosphoryl Transfer in Related Protein Tyrosine Phosphatases
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 prote...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2013-08, Vol.341 (6148), p.899-903 |
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| creator | Whittier, Sean K. Hengge, Alvan C. Loria, J. Patrick |
| description | 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. |
| doi_str_mv | 10.1126/science.1241735 |
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Patrick</creatorcontrib><title>Conformational Motions Regulate Phosphoryl Transfer in Related Protein Tyrosine Phosphatases</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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. 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| subjects | Bacterial Outer Membrane Proteins - chemistry Biochemistry Catalysis Catalysts Catalytic Domain Chemical equilibrium Chemistry Cleavage Closures DNA Enzymes HIV Humans Hydrolysis Interferons Kinetics Motion Nuclear Magnetic Resonance, Biomolecular Phosphates Phosphates - chemistry Phosphorus content Protein Conformation Protein Tyrosine Phosphatase, Non-Receptor Type 1 - chemistry Protein Tyrosine Phosphatases - chemistry Proteins Retroviridae Tuning Tyrosine Vanadates - chemistry |
| title | Conformational Motions Regulate Phosphoryl Transfer in Related Protein Tyrosine Phosphatases |
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