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Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires

Contakes, Stephen M. and Juda, Gregory A. and Langley, David B. and Halpern-Manners, Nicholas W. and Duff, Anthony P. and Dunn, Alexander R. and Gray, Harry B. and Dooley, David M. and Guss, J. Mitchell and Freeman, Hans C. (2005) Reversible inhibition of copper amine oxidase activity by channel-blocking ruthenium(II) and rhenium(I) molecular wires. Proceedings of the National Academy of Sciences of the United States of America, 102 (38). pp. 13451-13456. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:CONpnas05

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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 mu M 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.


Item Type:Article
Additional Information:Copyright © 2005 by the National Academy of Sciences. Contributed by Harry B. Gray, July 27, 2005. Published online before print September 12, 2005, 10.1073/pnas.0506336102. This work was supported by National Institutes of Health Grants GM65011 (to S.M.C.), DK19038 and GM070868 (both to H.B.G.), and GM27659 (to D.M.D.) and Australian Research Council Grant DP0208320 (to H.C.F. and J.M.G.). Data deposition: The coordinates and structure factors of the complex have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2BT3 [PDB]).
Subject Keywords:diimine; topaquinone; metalloenzyme; active site
Record Number:CaltechAUTHORS:CONpnas05
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:CONpnas05
Alternative URL:http://dx.doi.org/10.1073/pnas.0506336102
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2132
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Mar 2006
Last Modified:14 Nov 2014 19:19

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