Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires.
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.
Contakes
Stephen M
SM
Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Juda
Gregory A
GA
Langley
David B
DB
Halpern-Manners
Nicholas W
NW
Duff
Anthony P
AP
Dunn
Alexander R
AR
Gray
Harry B
HB
Dooley
David M
DM
Guss
J Mitchell
JM
Freeman
Hans C
HC
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
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D012211:Rhenium; D012428:Ruthenium; D006631:Amine Oxidase (Copper-Containing)