title: Crystal structure of activated ModE reveals conformational changes involving both oxyanion and DNA-binding domains.
abstract: ModE is a bacterial transcriptional regulator that orchestrates many aspects of molybdenum metabolism by binding to specific DNA sequences in a molybdate-dependent fashion. We present the crystal structure of Escherichia coli ModE in complex with molybdate, which was determined at 2.75A from a merohedrally twinned crystal (twin fraction approximately 0.30) with space group P4(3). We now have structures of ModE in both its "switched on" (ligand-bound) and "switched off" (apo) states. Comparison with the apo structure shows that ligand binding leads to extensive conformational changes not only in the molybdate-binding domain, but also in the DNA-binding domain. The most obvious difference is the loss of the pronounced asymmetry between the two chains of the ModE dimer, which had been a characteristic property of the apo structure. Another major change concerns the relative orientation of the two DNA-interacting winged helix-turn-helix motifs. Manual docking of an idealized DNA structure suggests that this conformational change should improve DNA binding of the activated molybdate-bound ModE.
authors.affiliation: Division of Biological Chemistry and Molecular Microbiology, The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Schüttelkopf
authors.forename: David H
authors.initials: DH
authors.lastname: Boxer
authors.forename: William N
authors.initials: WN
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000378:metabolism; D001426:Bacterial Proteins; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D029968:Escherichia coli Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000838:Anions; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C491064:ModE protein, E coli; C101050:ModE protein, bacteria; D014157:Transcription Factors; D004247:DNA; D010100:Oxygen