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Mechanism of oxidat...
Mechanism of oxidative inactivation of human presequence protease by hydrogen peroxide
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Chen, Jue (författare)
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- Teixeira, Pedro Filipe (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Glaser, Elzbieta (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Levine, Rodney L. (författare)
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 77, s. 57-63
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The mitochondrial presequence protease (PreP) is a member of the pitrilysin class of metalloproteases. It degrades the mitochondrial targeting presequences of mitochondria-localized proteins as well as unstructured peptides such as amyloid-beta peptide. The specific activity of PreP is reduced in Alzheimer patients and animal models of Alzheimer disease. The loss of activity can be mimicked in vitro by exposure to oxidizing conditions, and indirect evidence suggested that inactivation was due to methionine oxidation. We performed peptide mapping analyses to elucidate the mechanism of inactivation. None of the 24 methionine residues in recombinant human PreP was oxidized. We present evidence that inactivation is due to oxidation of cysteine residues and consequent oligomerization through intermolecular disulfide bonds. The most susceptible cysteine residues to oxidation are Cys34, Cys112, and Cys119. Most, but not all, of the activity loss is restored by the reducing agent dithiothreitol. These findings elucidate a redox mechanism for regulation of PreP and also provide a rational basis for therapeutic intervention in conditions characterized by excessive oxidation of PreP.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Presequence protease
- Protein oxidation
- Peptide degradation
- Cysteine oxidation
- Methionine sulfoxide
- Free radicals
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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