title: Crystal structure of the zinc-dependent MarR family transcriptional regulator AdcR in the Zn(II)-bound state.
abstract: Streptococcus pneumoniae adhesin competence regulator (AdcR), the first metal-dependent member of the multiple antibiotic resistance regulator (MarR) family of proteins, represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The 2.0 Å resolution structure of Zn(II)-bound AdcR reveals a highly helical two-fold-symmetric dimer with two distinct metal-binding sites per protomer. Zn(II) is tetrahedrally coordinated by E24, H42, H108, and H112 in what defines the primary sensing site in AdcR. Site 2 is a tetracoordinate site whose function is currently unknown. NMR methyl group perturbation experiments reveal that Zn(II) drives a global change in the structure of apo-AdcR that stabilizes a conformation that is compatible with DNA binding. This co-repression mechanism is unprecedented in MarR transcriptional regulators.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Guerra
authors.forename: Charles E
authors.initials: CE
authors.lastname: Dann
authors.forename: David P
authors.initials: DP
authors.lastname: Giedroc
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015032:Zinc
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