title: Intradomain LexA rotation is a prerequisite for DNA binding specificity.
abstract: In the absence of DNA damage the LexA protein represses the bacterial SOS system. We performed molecular dynamic simulations of two LexA dimers bound to operators. Our model predicted that rotation of the LexA DNA binding domain, with respect to the dimerised C-terminal domain, is required for selective DNA binding. To confirm the model, double and quadruple cysteine LexA mutants were engineered. Electrophoretic mobility-shift assay and surface plasmon resonance showed that disulfide bond formation between the introduced cysteine residues precluded LexA specific DNA binding due to blocked domain reorientation. Our model could provide the basis for novel drug design.
authors: Department of Biology, Biotechnical Faculty, University of Ljubljana, Vecna pot 111, Ljubljana, Slovenia. matej.butala@bf.uni-lj.si
authors: Matej
authors: M
authors: Butala
authors: Milan
authors: M
authors: Hodoscek
authors: Gregor
authors: G
authors: Anderluh
authors: Zdravko
authors: Z
authors: Podlesek
authors: Darja
authors: D
authors: Zgur-Bertok
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003087:Colicins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D008958:Models, Molecular; D009154:Mutation; D009875:Operator Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012399:Rotation; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D003087:Colicins; D004268:DNA-Binding Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein