Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange
- 30 January 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (3) , 956-961
- https://doi.org/10.1073/pnas.98.3.956
Abstract
Changes in protein mobility accompany changes in conformation during the trans-activation of enzymes; however, few studies exist that validate or characterize this behavior. In this study, amide hydrogen/deuterium exchange/mass spectrometry was used to probe the conformational flexibility of extracellular signal-regulated protein kinase-2 before and after activation by phosphorylation. The exchange data indicated that extracellular regulated protein kinase-2 activation caused altered backbone flexibility in addition to the conformational changes previously established by x-ray crystallography. The changes in flexibility occurred in regions involved in substrate binding and turnover, suggesting their importance in enzyme regulation.Keywords
This publication has 36 references indexed in Scilit:
- Catalytic Subunit of Cyclic AMP-Dependent Protein KinasePharmacology & Therapeutics, 1999
- Analysis of the relationship between enzyme activity and its internal motion using nuclear magnetic resonance: 15N relaxation studies of wild-type and mutant lysozymeJournal of Molecular Biology, 1999
- Deuterium Exchange Mass Spectrometry as a Probe of Protein Kinase Activation. Analysis of Wild-Type and Constitutively Active Mutants of MAP Kinase Kinase-1Biochemistry, 1998
- Activation Mechanism of the MAP Kinase ERK2 by Dual PhosphorylationCell, 1997
- A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibilityStructure, 1997
- NMR Study of Rapidly Exchanging Backbone Amide Protons in Staphylococcal Nuclease and the Correlation with Structural and Dynamic PropertiesJournal of the American Chemical Society, 1997
- Structure-based Calculation of the Equilibrium Folding Pathway of Proteins. Correlation with Hydrogen Exchange Protection FactorsJournal of Molecular Biology, 1996
- Mass spectrometric measurement of protein amide hydrogen exchange rates of apo‐ and holo‐myoglobinProtein Science, 1994
- Structure of a Peptide Inhibitor Bound to the Catalytic Subunit of Cyclic Adenosine Monophosphate-Dependent Protein KinaseScience, 1991
- A nuclear magnetic resonance study of the hydrogen-exchange behaviour of lysozyme in crystals and solutionJournal of Molecular Biology, 1991