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PMID: 11158577 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 3 ·2001-01-30 ·Pages 956-61

Hoofnagle AN, Resing KA, Goldsmith EJ, Ahn NG

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.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Binding Sites Hydrogen Bonding Ligands Mitogen-Activated Protein Kinase 1/chemistry,metabolism Models, Molecular Peptide Fragments/chemistry,metabolism Phosphorylation Protein Conformation Protein Structure, Secondary Rats Recombinant Proteins/chemistry,metabolism
Chemicals
Ligands Peptide Fragments Recombinant Proteins Adenosine Triphosphate Mitogen-Activated Protein Kinase 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hoofnagle A N
Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309, USA. ahn@spot.colorado.edu
Resing K A
Goldsmith E J
Ahn N G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.98.3.956
Email
ahn@spot.colorado.edu
Published
2001-01-30
Pages
956-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC14691
Subset
IM
Grants
NIGMS NIH HHS · GM08497 · United States
NIDDK NIH HHS · DK46993 · United States
NIGMS NIH HHS · T32 GM008497 · United States
NIGMS NIH HHS · R01 GM048521 · United States
NIGMS NIH HHS · GM48521 · United States
NIDDK NIH HHS · R01 DK046993 · United States
External Links
PubMed source DOI: 10.1073/pnas.98.3.956 PMC Full Text View journal details
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