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

Andrew N. Hoofnagle, Katheryn A. Resing, Elizabeth J. Goldsmith, Natalie G. Ahn

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)956-961
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number3
DOIs
StatePublished - Jan 30 2001

Fingerprint

Protein Kinases
Hydrogen
Crystallography
Enzyme Activation
Deuterium
Mitogen-Activated Protein Kinase 1
Amides
Mass Spectrometry
Proteins
Phosphorylation
X-Rays
Enzymes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{223f8777eecd4ebaa5d5182d6dc2fb40,
title = "Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange",
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.",
author = "Hoofnagle, {Andrew N.} and Resing, {Katheryn A.} and Goldsmith, {Elizabeth J.} and Ahn, {Natalie G.}",
year = "2001",
month = "1",
day = "30",
doi = "10.1073/pnas.98.3.956",
language = "English (US)",
volume = "98",
pages = "956--961",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "3",

}

TY - JOUR

T1 - Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange

AU - Hoofnagle, Andrew N.

AU - Resing, Katheryn A.

AU - Goldsmith, Elizabeth J.

AU - Ahn, Natalie G.

PY - 2001/1/30

Y1 - 2001/1/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035969987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035969987&partnerID=8YFLogxK

U2 - 10.1073/pnas.98.3.956

DO - 10.1073/pnas.98.3.956

M3 - Article

VL - 98

SP - 956

EP - 961

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 3

ER -