title: Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance.
abstract: Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria. Interestingly, several clinically relevant and human pathogenic strains are inherently resistant towards lantibiotics. The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator. Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain. The C-terminal domain exhibits a fold that classifies NsrR as a member of the OmpR/PhoB subfamily of regulators. Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators. Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.
authors.affiliation: Institute of Biochemistry, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Khosa
authors.affiliation: X-Ray Facility and Crystal Farm, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hoeppner
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Gohlke
authors.affiliation: Institute of Biochemistry, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.affiliation: Institute of Biochemistry, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225, Duesseldorf, Germany.
authors.forename: Sander H J
authors.initials: SH
authors.lastname: Smits
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000494:pharmacology*; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D004247:DNA