Structural study of TcaR and its complexes with multiple antibiotics from Staphylococcus epidermidis

• DOI: 10.1073/pnas.0913302107
• Publication Date: 2010-04-27T01:49:06Z
• Authors: Yu-Ming Chang; Wen-Yih Jeng; Tzu-Ping Ko; Yao-Jen Yeh; Cammy K.-M. Chen; Andrew H.-J. Wang
• Keywords: DNA, Bacterial; Models, Molecular; 0301 basic medicine; Operator Regions, Genetic; Base Sequence; Molecular Sequence Data; Electrophoretic Mobility Shift Assay; Penicillin G; Crystallography, X-Ray; Ligands; Protein Structure, Secondary; Salicylates; Anti-Bacterial Agents; 3. Good health; Repressor Proteins; 03 medical and health sciences; Bacterial Proteins; Structural Homology, Protein; Biofilms; 616; Staphylococcus epidermidis; Humans; Apoproteins; Protein Binding

TcaR and IcaR are a weak strong negative regulator of transcription the ica locus, respectively, their presence prevents poly- N -acetylglucosamine production biofilm formation in Staphylococcus epidermidis . Although was shown to interact with promoter, precise binding region mechanism interaction remained unclear. Here we present 3D structure its apo form complex salicylate as well several aminoglycoside β-lactam antibiotics. A comparison native structures indicates that regulation involves large conformational change DNA-binding lobe. Here, deduced consensus sequence two [∼TTNNAA] hexamers embedded 16 bp for dimer. Six dimers bind specifically three approximately 33 segments close varying affinities, repressor activity is directly interfered by different classes natural antimicrobial compounds. We also found this study compounds tested were not only inhibit TcaR–DNA but further induce S. our vivo assay. The results support general antibiotics regulating thereby help understand effect antibiotic exposure on bacterial resistance through formation.