title: Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification.
abstract: The unique biophysical and electronic properties of cysteine make this molecule one of the most biologically critical amino acids in the proteome. The defining sulfur atom in cysteine is much larger than the oxygen and nitrogen atoms more commonly found in the other amino acids. As a result of its size, the valence electrons of sulfur are highly polarizable. Unique protein microenvironments favor the polarization of sulfur, thus increasing the overt reactivity of cysteine. Here, we provide a brief overview of the endogenous generation of reactive oxygen and electrophilic species and specific examples of enzymes and transcription factors in which the oxidation or covalent modification of cysteine in those proteins modulates their function. The perspective concludes with a discussion of cysteine chemistry and biophysics, the hard and soft acids and bases model, and the proposal of the Soft Cysteine Signaling Network: a hypothesis proposing the existence of a complex signaling network governed by layered chemical reactivity and cross-talk in which the chemical modification of reactive cysteine in biological networks triggers the reorganization of intracellular biochemistry to mitigate spikes in endogenous or exogenous oxidative or electrophilic stress.
authors.affiliation: Department of Chemistry, ‡Department of Biological Sciences, and §W. Harry Feinstone Center for Genomic Research, University of Memphis , 3700 Walker Avenue, Memphis, Tennessee 38152-3370, United States.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Wible
authors.affiliation: Department of Chemistry, ‡Department of Biological Sciences, and §W. Harry Feinstone Center for Genomic Research, University of Memphis , 3700 Walker Avenue, Memphis, Tennessee 38152-3370, United States.
authors.forename: Thomas R
authors.identifier: 0000-0001-8294-7975
authors.initials: TR
authors.lastname: Sutter
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D015227:Lipid Peroxidation; D010100:Oxygen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D011506:Proteins; D013438:Sulfhydryl Compounds; D003545:Cysteine; D010100:Oxygen