title: Why selenocysteine replaces cysteine in thioredoxin reductase: a radical hypothesis.
abstract: Thioredoxin reductases, important biological redox mediators for two-electron transfers, contain either 2 cysteines or a cysteine (Cys) and a selenocysteine (Sec) at the active site. The incorporation of Sec is metabolically costly, and therefore surprising. We provide here a rationale: in the case of an accidental one-electron transfer to a S-S or a S-Se bond during catalysis, a thiyl or a selanyl radical, respectively would be formed. The thiyl radical can abstract a hydrogen from the protein backbone, which subsequently leads to the inactivation of the protein. In contrast, a selanyl radical will not abstract a hydrogen. Therefore, formation of Sec radicals in a GlyCysSecGly active site will less likely result in the destruction of a protein compared to a GlyCysCysGly active site.
authors.affiliation: Institute of Inorganic Chemistry and ‡Institute of Physical Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich , Vladimir-Prelog-Weg 2, CH-8093 Zürich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nauser
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinmann
authors.forename: Guido
authors.initials: G
authors.lastname: Grassi
authors.forename: Willem H
authors.initials: WH
authors.lastname: Koppenol
mesh_terms: D020134:Catalytic Domain; D003545:Cysteine / Q000378:metabolism*; D008956:Models, Chemical; D011485:Protein Binding / Q000502:physiology; D012643:Selenium / Q000737:chemistry; D017279:Selenocysteine / Q000737:chemistry* / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry; D013816:Thermodynamics; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D017279:Selenocysteine; D013455:Sulfur; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium; D003545:Cysteine