title: Insights into substrate and metal binding from the crystal structure of cyanobacterial aldehyde deformylating oxygenase with substrate bound.
abstract: The nonheme diiron enzyme cyanobacterial aldehyde deformylating oxygenase, cADO, catalyzes the highly unusual deformylation of aliphatic aldehydes to alkanes and formate. We have determined crystal structures for the enzyme with a long-chain water-soluble aldehyde and medium-chain carboxylic acid bound to the active site. These structures delineate a hydrophobic channel that connects the solvent with the deeply buried active site and reveal a mode of substrate binding that is different from previously determined structures with long-chain fatty acids bound. The structures also identify a water channel leading to the active site that could facilitate the entry of protons required in the reaction. NMR studies examining 1-[(13)C]-octanal binding to cADO indicate that the enzyme binds the aldehyde form rather than the hydrated form. Lastly, the fortuitous cocrystallization of the metal-free form of the protein with aldehyde bound has revealed protein conformation changes that are involved in binding iron.
authors.affiliation: Department of Chemistry, ‡Life Sciences Institute, and §Department of Biological Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Buer
authors.forename: Bishwajit
authors.initials: B
authors.lastname: Paul
authors.forename: Debasis
authors.initials: D
authors.lastname: Das
authors.forename: Jeanne A
authors.initials: JA
authors.lastname: Stuckey
authors.forename: E Neil G
authors.initials: EN
authors.lastname: Marsh
mesh_terms: D000458:Cyanobacteria / Q000201:enzymology*; D008670:Metals / Q000378:metabolism*; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008670:Metals; D010105:Oxygenases