title: Crystal structure of a pH-regulated luciferase catalyzing the bioluminescent oxidation of an open tetrapyrrole.
abstract: The luciferase of Lingulodinium polyedrum, a marine bioluminescent dinoflagellate, consists of three similar but not identical domains in a single polypeptide. Each encodes an active luciferase that catalyzes the oxidation of a chlorophyll-derived open tetrapyrrole (dinoflagellate luciferin) to produce blue light. These domains share no sequence similarity with any other in the GenBank database and no structural or motif similarity with any other luciferase. We report here the 1.8-A crystal structure of the third domain, D3, at pH 8, and a mechanism for its activity regulation by pH. D3 consists of two major structural elements: a beta-barrel pocket putatively for substrate binding and catalysis and a regulatory three-helix bundle. N-terminal histidine residues previously shown to regulate activity by pH are at the interface of the helices in the bundle. Molecular dynamics calculations indicate that, in response to changes in pH, these histidines could trigger a large molecular motion of the bundle, thereby exposing the active site to the substrate.
authors.affiliation: Department of Structural Biology, Hauptman-Woodward Medical Research Institute, State University of New York, Buffalo, NY 14203, USA. schultz@hwi.buffalo.edu
authors.forename: L Wayne
authors.initials: LW
authors.lastname: Schultz
authors.forename: Liyun
authors.initials: L
authors.lastname: Liu
authors.forename: Margaret
authors.initials: M
authors.lastname: Cegielski
authors.forename: J Woodland
authors.initials: JW
authors.lastname: Hastings
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004141:Dinoflagellida / Q000201:enzymology*; D006639:Histidine; D006863:Hydrogen-Ion Concentration; D008156:Luciferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D045725:Tetrapyrroles / Q000378:metabolism*
chemical_list: D008164:Luminescent Proteins; D045725:Tetrapyrroles; D006639:Histidine; D008156:Luciferases