کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1178283 962679 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases
چکیده انگلیسی


• Kinetic isotope effects provide mechanistic information about phosphoryl transfer.
• The transition states of enzymatic and uncatalyzed phosphoryl transfer are similar.
• Different PTP catalysis rates are correlated with different rates of protein loop motion.
• Mutations to noncatalytic residues in PTPs affect loop motion and general acid catalysis.

Although thermodynamically favorable, the uncatalyzed hydrolysis of phosphate monoesters is extraordinarily slow, making phosphatases among the most catalytically efficient enzymes known. Protein-tyrosine phosphatases (PTPs) are ubiquitous in biology, and kinetic isotope effects were one of the key mechanistic tools used to discern molecular details of their catalytic mechanism and the transition state for phosphoryl transfer. Later, the unique level of detail KIEs provided led to deeper questions about the potential role of protein motions in PTP catalysis. The recent discovery that such motions are responsible for different catalytic rates between PTPs arose from questions originating from KIE data showing that the transition states and chemical mechanisms are identical, combined with structural data demonstrating superimposable active sites. KIEs also reveal perturbations to the transition state as mutations are made to residues directly involved in chemistry, and to residues that affect protein motions essential for catalysis.This article is part of a Special Issue entitled: Enzyme Transition States from Theory and Experiment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1854, Issue 11, November 2015, Pages 1768–1775
نویسندگان
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