title: Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial pathogen interface.
abstract: Hosts employ myriad weapons to combat invading microorganisms as an integral feature of the host-bacterial pathogen interface. This interface is dominated by highly reactive small molecules that collectively induce oxidative stress. Successful pathogens employ transcriptional regulatory proteins that sense these small molecules directly or indirectly via a change in the ratio of reduced to oxidized low-molecular weight (LMW) thiols that collectively comprise the redox buffer in the cytoplasm. These transcriptional regulators employ either a prosthetic group or reactive cysteine residue(s) to effect changes in the transcription of genes that encode detoxification and repair systems that is driven by regulator conformational switching between high-affinity and low-affinity DNA-binding states. Cysteine harbors a highly polarizable sulfur atom that readily undergoes changes in oxidation state in response to oxidative stress to produce a range of regulatory post-translational modifications (PTMs), including sulfenylation (S-hydroxylation), mixed disulfide bond formation with LMW thiols (S-thiolation), di- and trisulfide bond formation, S-nitrosation, and S-alkylation. Here we discuss several examples of structurally characterized cysteine thiol-specific transcriptional regulators that sense changes in cellular redox balance, focusing on the nature of the cysteine PTM itself and the interplay of small molecule oxidative stressors in mediating a specific transcriptional response.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405-7102, United States.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Luebke
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405-7102, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Giedroc
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism* / Q000503:physiopathology; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D013455:Sulfur; D003545:Cysteine