title: Thiol/Disulfide redox switches in the regulation of heme binding to proteins.
abstract: This review focuses on thiol/disulfide redox switches that regulate heme binding to proteins and modulate their activities. The importance of redox switches in metabolic regulation and the general mechanism by which redox switches modulate activity are discussed. Methods are described to characterize heme-binding sites and to assess their physiological relevance. For thiol/disulfide interconversion to regulate activity of a system, the redox process must be reversible at the ambient redox potentials found within the cell; thus, methods (and their limitations) are discussed that can address the physiological relevance of a redox switch. We review recent results that define a mechanism for how thiol/disulfide redox switches that control heme binding can regulate the activities of an enzyme, heme oxygenase-2, and an ion channel, the BK potassium channel. The redox switches on these proteins are composed of different types of Cys-containing motifs that have opposite effects on heme affinity, yet have complementary effects on hypoxia sensing. Finally, a model is proposed to describe how the redox switches on heme oxygenase-2 and the BK channel form an interconnected system that is poised to sense oxygen levels in the bloodstream and to elicit the hypoxic response when oxygen levels drop below a threshold value.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0606, USA. sragsdal@umich.edu
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
authors.forename: Li
authors.initials: L
authors.lastname: Yi
mesh_terms: D004220:Disulfides / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
chemical_list: D004220:Disulfides; D011506:Proteins; D006418:Heme
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