Relative strengths of Se⋯N,O interactions: Implications for glutathione peroxidase activity

Bayse, Craig A.; Baker, Renee A.; Ortwine, Kristine

doi:10.1016/j.ica.2005.06.075

Cited by 38 publications

(31 citation statements)

References 23 publications

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“…In amides, the carbonyl oxygen is more Lewis basic than the nitrogen due to the resonance structures. Based upon our calculations, we predicted that the Gln residue in the catalytic triad of GPx would form Se···Ointeractions with the Se-OH and Se-SG intermediates rather than the Se···Ninteraction expected from earlier discussions (46). However, Morokuma later showed that neither interaction is favored in their DFT models of the GPx active site (59).…”

Section: Scheme 1 Mechanism For Redox Scavenging By Gpx and Other Sementioning

confidence: 67%

“…Experimental study of the mechanisms of these compounds is made difficult by the instability of key intermediates and the complex nature of the mechanisms. Early on, we sought to relate the GPx activity of known mimics to the strength of their Se···N,Ointeractions through a series of DFT calculations (46). In terms of valence bond theory (47), the resonance structures for the donation of a pair of electrons from L to an Se-X bond can be written for the interaction similar to a three-center-four-electron hypervalent bond (eq 2).…”

Section: Scheme 1 Mechanism For Redox Scavenging By Gpx and Other Sementioning

confidence: 99%

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Modeling of Mechanisms of Selenium Bioactivity Using Density Functional Theory

Bayse

2013

ACS Symposium Series

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Selenium plays an important role in normal biological function through its incorporation into processes that protect against oxidative stress and promote thyroid function. The complex nature of the mechanisms involved has led to extensive study through computational modeling. However, density functional theory (DFT) modeling of the redox mechanisms of selenium is complicated by proton exchange processes catalyzed by the bulk solvent. To address this issue, we have used a method of microsolvation which we have dubbed solvent-assisted proton exchange (SAPE). These models include a few strategically placed water molecules to act as a proton shuttle and are able to obtain activation barriers that are in good agreement with experimental data and trends. Models that do not use these networks necessarily have higher barriers because they force the proton exchange through an 'unnatural' pathway that is not representative of the reaction as it occurs in solution. As a first approximation to solution-phase reactivity, SAPE models are more appropriate for drawing conclusions about the trends and energetics of these complex mechanisms. From these models, we have gained significant insight into the biological pathways of these compounds. In this chapter, we discuss our implementation of SAPE models for redox scavenging by various biorelevant organoselenium compounds, specifically arylselenols, seleninic acids and ebselen, and the related mechanism of cysteine. Finally, we discuss approaches to modeling additional important biochalcogen processes in the thyroid and in zinc finger proteins.

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Section: Scheme 1 Mechanism For Redox Scavenging By Gpx and Other Sementioning

confidence: 67%

Section: Scheme 1 Mechanism For Redox Scavenging By Gpx and Other Sementioning

confidence: 99%

Modeling of Mechanisms of Selenium Bioactivity Using Density Functional Theory

Bayse

2013

ACS Symposium Series

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“…Donation to the σ S‐S/Se * LUMO by weaker donors could protect against reduction by blocking the incoming thiol. When the disulfide/selenosulfide is in the g(+)g(+)t configuration, the carbonyl oxygen of Cys4 can form an S/Se···O intramolecular interaction by donating its lone pair to σ S‐S/Se *. The interaction blocks the approach of a reducing nucleophile at Se and destabilizes σ S‐S/Se * to decrease the electrophilicity of the S‐S/Se bond (Tables S1‐S3).…”

Section: Resultsmentioning

confidence: 99%

Conformation dynamics of cyclic disulfides and selenosulfides in CXXC(U) (X = Gly, Ala) tetrapeptide redox motifs

Bayse

Pollard

2019

Journal of Peptide Science

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Thioredoxin fold proteins often contain a Cys‐(Xxx)n‐Cys(Sec) or CXnC(U) motif, where the active cysteine (C) or selenocysteine (U) is bridged by X residues, which vary with protein function. The effect of the X residues on the conformation space of the oxidized disulfide and selenosulfide forms of the CXXC(U) motif has been investigated using molecular dynamics (MD) and density functional theory. Multi‐microsecond‐length MD simulations of the CGGC, CGAC, and CAGC cyclic peptides show that CGGC rings readily exchange between several conformations over the course of the simulation, but steric interactions with the methyl group of Ala limit the conformation space available to the cyclic peptide, especially for CGAC. The potential for the motif to be reduced, as measured by the energy of the lowest unoccupied molecular orbitals, is dependent upon the ring conformation. These results suggest that control of available conformations by the bridging residues and the protein tertiary structure may be important for defining the function of the CXXC motif. Theoretical 77Se chemical shifts of the selenosulfide moiety are dependent upon the conformation and/or intramolecular Se···O interactions with the backbone carbonyl group of the C‐terminal U residue.

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“…It was showed that the minerals were beneficial not only to the growth of yeast but also to the synthesis of organic Se in yeast. As Se was a biomass related product, the increase of biomass enhance the activity of the most important selenic enzyme -Glutathione Peroxidase (GSH-Px) (Abdel Rahim, 2005;Bayse, Baker, & Ortwine, 2005), which is critical for survival and function of aerobic organisms because it can effectively inhibit oxidation and prolong life of the organism.…”

Section: Response Surfaces Analysesmentioning

confidence: 99%