The role of cysteines in the structure and function of OGG1

Wang, Katarina; Maayah, Marah; Sweasy, Joann B.; Alnajjar, Khadijeh S.

doi:10.1074/jbc.ra120.016126

Cited by 33 publications

(33 citation statements)

References 57 publications

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“…A putative regulatory role of the detected NOS/SONOS redox switches is further supported by the high degree of conservation of the lysine–cysteine pairs in the protein orthologs (either across different domains of life or in clades of related organisms) despite the fact that in many proteins, only one of the two residues has a direct functional role required for biological activity, as reported for, for example, OGG1 or rabphilin (Supplementary Figs. 5 and 6 ) 33 , 34 .…”

Section: Resultsmentioning

confidence: 99%

Widespread occurrence of covalent lysine–cysteine redox switches in proteins

et al. 2022

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We recently reported the discovery of a lysine–cysteine redox switch in proteins with a covalent nitrogen–oxygen–sulfur (NOS) bridge. Here, a systematic survey of the whole protein structure database discloses that NOS bridges are ubiquitous redox switches in proteins of all domains of life and are found in diverse structural motifs and chemical variants. In several instances, lysines are observed in simultaneous linkage with two cysteines, forming a sulfur–oxygen–nitrogen–oxygen–sulfur (SONOS) bridge with a trivalent nitrogen, which constitutes an unusual native branching cross-link. In many proteins, the NOS switch contains a functionally essential lysine with direct roles in enzyme catalysis or binding of substrates, DNA or effectors, linking lysine chemistry and redox biology as a regulatory principle. NOS/SONOS switches are frequently found in proteins from human and plant pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and also in many human proteins with established roles in gene expression, redox signaling and homeostasis in physiological and pathophysiological conditions.

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Section: Resultsmentioning

confidence: 99%

Widespread occurrence of covalent lysine–cysteine redox switches in proteins

et al. 2022

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“…These data suggest that OGG1 could play a protective role in inflammatory diseases. OGG1 polymorphism could offer susceptibility to lupus nephritis and modulate 8-OH-d G serum level in SLE patients [ 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

“…High SLEDAI was correlated with low serum albumin in lupus nephritis [ 15 ]. Some studies in the last few years showed that thiol-disulfides interconversion plays a crucial role in antioxidant defense, apoptosis, detoxification, transcription, enzymatic activity regulation [ 20 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Ene

Georgescu

Tampa

et al. 2021

JPM

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The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

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“…A putative regulatory role of the detected NOS/SONOS redox switches is further supported by the high degree of conservation of the lysine-cysteine pairs in the protein orthologues (either across different domains of life or in clades of related organisms) despite the fact that in many proteins only one of the two residues has a direct functional role required for biological activity as reported for e.g. OGG1 or rabphilin (SI Tables 3, 4) 30,31 .…”

Section: Chemical Functions Of the Nos Lysine And Cysteine Residuesmentioning

confidence: 67%

NOS and SONOS redox switches in proteins

Pappenheim

Wensien

Jin

et al. 2021

Preprint

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We recently reported on the discovery of a lysine-cysteine redox switch in proteins with a covalent NOS bridge. Here, a systematic survey of the whole protein structure database discloses that NOS bridges are ubiquitous, hitherto overlooked redox switches in proteins of all domains of life and are found in diverse structural motifs and chemical variants. In several instances, lysines are observed in simultaneous linkage with two cysteines forming a SONOS bridge with a trivalent nitrogen, which constitutes the first native branching crosslink in proteins. In many proteins, the NOS switch contains a functionally essential lysine with direct roles in enzyme catalysis or binding of substrates, DNA or effectors linking lysine chemistry and redox biology as a novel regulatory principle. The NOS/SONOS switches are frequently found in proteins from human and plant pathogens including i.a. SARS-CoV-2 but also in many human proteins with established roles in gene expression, redox signaling and homeostasis in both physiological and pathophysiological conditions. Targeting, mimicking, controlling and engineering the NOS and SONOS redox switches appear to open novel avenues in drug, antiviral, antibiotic and herbicide development, in biocatalytic applications as well as in protein design and bioorganic chemistry.

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The role of cysteines in the structure and function of OGG1

Cited by 33 publications

References 57 publications

Widespread occurrence of covalent lysine–cysteine redox switches in proteins

Widespread occurrence of covalent lysine–cysteine redox switches in proteins

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

NOS and SONOS redox switches in proteins

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