Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase

Andre L. Samson; Anja S. Knaupp; Itamar Kass; Oded Kleifeld; Emilia M. Marijanovic; Victoria A. Hughes; Chris J. Lupton; Ashley M. Buckle; Stephen P. Bottomley; Robert L. Medcalf

doi:10.1074/jbc.M114.570275

Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase

Andre L. Samson, Anja S. Knaupp, Itamar Kass, Oded Kleifeld, Emilia M. Marijanovic, Victoria A. Hughes, Chris J. Lupton, Ashley M. Buckle, Stephen P. Bottomley, Robert L. Medcalf

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Background: GAPDH is a glycolytic enzyme that aggregates during disease. Cysteine oxidation is the putative cause of aggregation. Whether GAPDH aggregation influences disease is unknown.

Results: Mutating Met-46 renders GAPDH resistant to free radical-induced aggregation.

Conclusion: Methionine oxidation, rather than cysteine oxidation, is a primary event that instigates GAPDH aggregation.

Significance: Mutating Met-46 in vivo should elucidate whether GAPDH aggregation causally contributes to disease.

Original language	English
Pages (from-to)	26922-26936
Number of pages	15
Journal	Journal of Biological Chemistry
Volume	289
Issue number	39
DOIs	https://doi.org/10.1074/jbc.M114.570275
State	Published - 26 Sep 2014
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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@article{e53481619f654e1ab5637252f1f9ac9b,

title = "Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase",

abstract = "Background: GAPDH is a glycolytic enzyme that aggregates during disease. Cysteine oxidation is the putative cause of aggregation. Whether GAPDH aggregation influences disease is unknown.Results: Mutating Met-46 renders GAPDH resistant to free radical-induced aggregation.Conclusion: Methionine oxidation, rather than cysteine oxidation, is a primary event that instigates GAPDH aggregation.Significance: Mutating Met-46 in vivo should elucidate whether GAPDH aggregation causally contributes to disease.",

author = "Samson, \{Andre L.\} and Knaupp, \{Anja S.\} and Itamar Kass and Oded Kleifeld and Marijanovic, \{Emilia M.\} and Hughes, \{Victoria A.\} and Lupton, \{Chris J.\} and Buckle, \{Ashley M.\} and Bottomley, \{Stephen P.\} and Medcalf, \{Robert L.\}",

note = "Publisher Copyright: {\textcopyright} 2014 by The American Society for Biochemistry and Molecular Biology, Inc.",

year = "2014",

month = sep,

day = "26",

doi = "10.1074/jbc.M114.570275",

language = "English",

volume = "289",

pages = "26922--26936",

journal = "Journal of Biological Chemistry",

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TY - JOUR

T1 - Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase

AU - Samson, Andre L.

AU - Knaupp, Anja S.

AU - Kass, Itamar

AU - Kleifeld, Oded

AU - Marijanovic, Emilia M.

AU - Hughes, Victoria A.

AU - Lupton, Chris J.

AU - Buckle, Ashley M.

AU - Bottomley, Stephen P.

AU - Medcalf, Robert L.

PY - 2014/9/26

Y1 - 2014/9/26

N2 - Background: GAPDH is a glycolytic enzyme that aggregates during disease. Cysteine oxidation is the putative cause of aggregation. Whether GAPDH aggregation influences disease is unknown.Results: Mutating Met-46 renders GAPDH resistant to free radical-induced aggregation.Conclusion: Methionine oxidation, rather than cysteine oxidation, is a primary event that instigates GAPDH aggregation.Significance: Mutating Met-46 in vivo should elucidate whether GAPDH aggregation causally contributes to disease.

AB - Background: GAPDH is a glycolytic enzyme that aggregates during disease. Cysteine oxidation is the putative cause of aggregation. Whether GAPDH aggregation influences disease is unknown.Results: Mutating Met-46 renders GAPDH resistant to free radical-induced aggregation.Conclusion: Methionine oxidation, rather than cysteine oxidation, is a primary event that instigates GAPDH aggregation.Significance: Mutating Met-46 in vivo should elucidate whether GAPDH aggregation causally contributes to disease.

UR - https://www.scopus.com/pages/publications/84907454948

U2 - 10.1074/jbc.M114.570275

DO - 10.1074/jbc.M114.570275

M3 - Article

C2 - 25086035

AN - SCOPUS:84907454948

SN - 0021-9258

VL - 289

SP - 26922

EP - 26936

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 39

ER -

Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase

Abstract

ASJC Scopus subject areas

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