Methionine residues as endogenous antioxidants in proteins

Levine, Rodney L.; Mosoni, Laurent; Berlett, Barbara S.; Stadtman, Earl R.

doi:10.1073/pnas.93.26.15036

Cited by 973 publications

(802 citation statements)

References 27 publications

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“…Methionine (Levine et al, 1996) and cysteine residues are thought to act as antioxidants by directly scavenging ROS; both amino acids are particularly susceptible to oxidative stress; however, unlike most protein oxidations, these modifications are reversible. Free and protein bound methionine can be cycled between the oxidized and reduced forms with the aid of the Msr enzymes (Levine et al, 1996).…”

Section: Mitochondrial Reducing Systemsmentioning

confidence: 99%

“…Free and protein bound methionine can be cycled between the oxidized and reduced forms with the aid of the Msr enzymes (Levine et al, 1996). Protein bound cysteine residues are known to be key players in redox sensing and regulation (Holmgren et al, 2005), and there are a number of repair systems for disulphide bonds, cycling of cysteine residues between oxidized and reduced forms.…”

Section: Mitochondrial Reducing Systemsmentioning

confidence: 99%

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Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

161

141

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Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

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Section: Mitochondrial Reducing Systemsmentioning

confidence: 99%

Section: Mitochondrial Reducing Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

161

141

View full text Add to dashboard Cite

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“…6 [63]. The cyclic oxidation-reduction of methionine through NADPH-dependant thioredoxin reductase is an important antioxidant mechanism [64][65][66][67]. Agedependent increase in methionine sulphoxide content of proteins was reported for different tissues, notably erythrocytes [67].…”

Section: Protein Thiols and Thioethersmentioning

confidence: 99%

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Barelli

Canellini

Thadikkaran

et al. 2008

Proteomics Clinical Apps

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Protein oxidation mechanisms result in a wide array of modifications, from backbone cleavage or protein crosslinking to more subtle modifications such as side chain oxidations. Protein oxidation occurs as part of normal regulatory processes, as a defence mechanism against oxidative stress, or as a deleterious processes when antioxidant defences are overcome. Because blood is continually exposed to reactive oxygen and nitrogen species, blood proteomics should inherently adopt redox proteomic strategies. In this review, we recall the biochemical basis of protein oxidation, review the proteomic methodologies applied to analyse redox modifications, and highlight some physiological and in vitro responses to oxidative stress of various blood components.

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“…42 The oxidation of such Met residues can lead to conformational changes that result in the exposure of previously unexposed hydrophobic residues. 43,44 In other words, the oxidation of different Met residues on a protein may not be independent of each other. However, a detailed understanding of the mechanisms behind such correlations is still lacking.…”

Section: Discussionmentioning

confidence: 99%

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

Sankar¹,

Hoi²,

Yuan

et al. 2018

mAbs

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Monoclonal antibodies (mAbs) have become a major class of protein therapeutics that target a spectrum of diseases ranging from cancers to infectious diseases. Similar to any protein molecule, mAbs are susceptible to chemical modifications during the manufacturing process, long-term storage, and in vivo circulation that can impair their potency. One such modification is the oxidation of methionine residues. Chemical modifications that occur in the complementarity-determining regions (CDRs) of mAbs can lead to the abrogation of antigen binding and reduce the drug’s potency and efficacy. Thus, it is highly desirable to identify and eliminate any chemically unstable residues in the CDRs during the therapeutic antibody discovery process. To provide increased throughput over experimental methods, we extracted features from the mAbs’ sequences, structures, and dynamics, used random forests to identify important features and develop a quantitative and highly predictive in silico methionine oxidation model.

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Methionine residues as endogenous antioxidants in proteins

Cited by 973 publications

References 27 publications

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

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