title: Does the Transcription Factor NemR Use a Regulatory Sulfenamide Bond to Sense Bleach?
abstract: Reactive chlorine species (RCS), such as hypochlorous acid (i.e., bleach), are antimicrobial oxidants produced by the innate immune system. Like many redox-regulated transcription factors, the Escherichia coli repressor NemR responds to RCS by using the reversible oxidation of highly conserved cysteines to alter its DNA-binding affinity. However, earlier work showed that RCS response in NemR does not depend on any commonly known oxidative cysteine modifications. We have now determined the crystal structure of NemR, showing that the regulatory cysteine, Cys106, is in close proximity to a highly conserved lysine (Lys175). We used crystallographic, biochemical, and mass spectrometric analyses to analyze the role of this lysine residue in RCS sensing. Based on our results, we hypothesize that RCS treatment of NemR results in the formation of a reversible Cys106-Lys175 sulfenamide bond. This is, to our knowledge, the first description of a protein whose function is regulated by a cysteine-lysine sulfenamide thiol switch, constituting a novel addition to the biological repertoire of functional redox switches.
authors: 1 Department of Molecular, Cellular, and Developmental Biology, University of Michigan , Ann Arbor, Michigan.
authors: Michael Jeffrey
authors: MJ
authors: Gray
authors: 2 Life Sciences Institute, University of Michigan , Ann Arbor, Michigan.
authors: Yan
authors: Y
authors: Li
authors: 3 Institute of Biochemistry and Pathobiochemistry-Microbial Biochemistry, Ruhr-Universität Bochum , Bochum, Germany .
authors: Lars Ingo-Ole
authors: LI
authors: Leichert
authors: 2 Life Sciences Institute, University of Michigan , Ann Arbor, Michigan.|4 Department of Biological Chemistry, Medical School, University of Michigan , Ann Arbor, Michigan.
authors: Zhaohui
authors: Z
authors: Xu
authors: 1 Department of Molecular, Cellular, and Developmental Biology, University of Michigan , Ann Arbor, Michigan.
authors: Ursula
authors: U
authors: Jakob
mesh_terms: D003545:Cysteine / Q000737:chemistry; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D010084:Oxidation-Reduction; D013416:Sulfamerazine / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C531319:NemR protein, E coli; D014157:Transcription Factors; C471392:sulfenamide; D006997:Hypochlorous Acid; D008239:Lysine; D003545:Cysteine; D013416:Sulfamerazine