title: Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires.
abstract: Molecular wires comprising a Ru(II)- or Re(I)-complex head group, an aromatic tail group, and an alkane linker reversibly inhibit the activity of the copper amine oxidase from Arthrobacter globiformis (AGAO), with K(i) values between 6 muM and 37 nM. In the crystal structure of a Ru(II)-wire:AGAO conjugate, the wire occupies the AGAO active-site substrate access channel, the trihydroxyphenylalanine quinone cofactor is ordered in the "off-Cu" position with its reactive carbonyl oriented toward the inhibitor, and the "gate" residue, Tyr-296, is in the "open" position. Head groups, tail-group substituents, and linker lengths all influence wire-binding interactions with the enzyme.
authors.affiliation: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Contakes
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Juda
authors.forename: David B
authors.initials: DB
authors.lastname: Langley
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Halpern-Manners
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Duff
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Dunn
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: David M
authors.initials: DM
authors.lastname: Dooley
authors.forename: J Mitchell
authors.initials: JM
authors.lastname: Guss
authors.forename: Hans C
authors.initials: HC
authors.lastname: Freeman
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry* / Q000378:metabolism; D001173:Arthrobacter / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012211:Rhenium / Q000737:chemistry* / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D012211:Rhenium; D012428:Ruthenium; D006631:Amine Oxidase (Copper-Containing)