title: A model for the LexA repressor DNA complex.
abstract: A structural model for the interaction of the LexA repressor DNA binding domain (DBD) with operator DNA is derived by means of Monte Carlo docking. Protein-DNA complexes were generated by docking the LexA repressor DBD NMR solution structure onto both rigid and bent B-DNA structures while giving energy bonuses for contacts in agreement with experimental data. In the resulting complexes, helix III of the LexA repressor DBD is located in the major groove of the DNA and residues Asn-41, Glu-44, and Glu-45 form specific hydrogen bonds with bases of the CTGT DNA sequence. Ser-39, Ala-42, and Asn-41 are involved in a hydrophobic interaction with the methyl group of the first thymine base. Residues in the loop region connecting the two beta-sheet strands are involved in nonspecific contacts near the dyad axis of the operator. The contacts observed in the docked complexes cover the entire consensus CTGT half-site DNA operator, thus explaining the specificity of the LexA repressor for such sequences. In addition, a large number of nonspecific interactions between protein and DNA is observed. The agreement between the derived model for the LexA repressor DBD/DNA complex and experimental biochemical results is discussed.
authors.affiliation: Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Knegtel
authors.forename: R H
authors.initials: RH
authors.lastname: Fogh
authors.forename: G
authors.initials: G
authors.lastname: Ottleben
authors.forename: H
authors.initials: H
authors.lastname: Rüterjans
authors.forename: P
authors.initials: P
authors.lastname: Dumoulin
authors.forename: M
authors.initials: M
authors.lastname: Schnarr
authors.forename: R
authors.initials: R
authors.lastname: Boelens
authors.forename: R
authors.initials: R
authors.lastname: Kaptein
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein