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RegB Kinase Activity Is Repressed by Oxidative Formation of Cysteine Sulfenic Acid |
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| Authors: | Jiang Wu Zhuo Cheng Khalilah Reddie Kate Carroll Loubna A Hammad Jonathan A Karty Carl E Bauer |
| Institution: | From the ‡Department of Molecular and Cellular Biochemistry and ;the ‖METACyt Biochemical Analysis Center, Department of Chemistry, Indiana University, Bloomington, Indiana 47405.;the §Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, and ;the ¶Department of Chemistry, The Scripps Research Institute, Florida Campus, Jupiter, Florida 33458 |
| Abstract: | RegB/RegA comprise a global redox-sensing signal transduction system utilized by a wide range of proteobacteria to sense environmental changes in oxygen tension. The conserved cysteine 265 in the sensor kinase RegB was previously reported to form an intermolecular disulfide bond under oxidizing conditions that converts RegB from an active dimer into an inactive tetramer. In this study, we demonstrate that a stable sulfenic acid (-SOH) derivative also forms at Cys-265 in vitro and in vivo when RegB is exposed to oxygen. This sulfenic acid modification is reversible and stable in the air. Autophosphorylation assay shows that reduction of the SOH at Cys-265 to a free thiol (SH) can increase RegB kinase activity in vitro. Our results suggest that a sulfenic acid modification at Cys-265 performs a regulatory role in vivo and that it may be the major oxidation state of Cys-265 under aerobic conditions. Cys-265 thus functions as a complex redox switch that can form multiple thiol modifications in response to different redox signals to control the kinase activity of RegB. |
| Keywords: | Bacterial Signal Transduction Gene Regulation Histidine Kinases Phosphorylation Redox Regulation RegB Sensor Kinase Sulfenic Acid |