title: A closer view of the conformation of the Lac repressor bound to operator.
abstract: Crystal structures of the Lac repressor, with and without isopropyithiogalactoside (IPTG), and the repressor bound to operator have provided a model for how the binding of the inducer reduces the affinity of the repressor for the operator. However, because of the low resolution of the operator-bound structure (4.8 A), the model for the allosteric transition was presented in terms of structural elements rather than in terms of side chain interactions. Here we have constructed a dimeric Lac repressor and determined its structure at 2.6 A resolution in complex with a symmetric operator and the anti-inducer orthonitrophenylfucoside (ONPF). The structure enables the induced (IPTG-bound) and repressed (operator-bound) conformations of the repressor to be compared in atomic detail. An extensive network of interactions between the DNA-binding and core domains of the repressor suggests a possible mechanism for the allosteric transition.
authors.affiliation: The Johnson Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton walk, Philadelphia, Pennsylvania 19102-6059, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Bell
authors.forename: M
authors.initials: M
authors.lastname: Lewis
mesh_terms: D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics; D029968:Escherichia coli Proteins; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007544:Isopropyl Thiogalactoside / Q000737:chemistry / Q000378:metabolism; D056968:Lac Repressors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009875:Operator Regions, Genetic / Q000235:genetics*; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D006027:Glycosides; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins; C047034:2-nitrophenyl-beta-fucoside; D007544:Isopropyl Thiogalactoside; D004247:DNA