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Enantiomer-Specific Binding of Ruthenium(II) Molecular Wires by the Amine Oxidase of Arthrobacter globiformis

Langley, David B. and Brown, Doreen E. and Cheruzel, Lionel E. and Contakes, Stephen M. and Duff, Anthony P. and Hilmer, Kimberly M. and Dooley, David M. and Gray, Harry B. and Guss, J. Mitchell and Freeman, Hans C. (2008) Enantiomer-Specific Binding of Ruthenium(II) Molecular Wires by the Amine Oxidase of Arthrobacter globiformis. Journal of the American Chemical Society, 130 (25). pp. 8069-8078. ISSN 0002-7863. PMCID PMC2518534. https://resolver.caltech.edu/CaltechAUTHORS:20170510-090742106

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[img] PDF (Closest contacts between the TPQ cofactor of the enzyme and the DMA tail group of the C4 wire (Table S1), CD spectra of Λ- and Δ-[DMA−C4−Ru(II)(phen)(bpy)2]2+ (Figure S1), and Lineweaver−Burk plots showing inhibition of CuAO (Figure S2)) - Supplemental Material
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Abstract

The copper amine oxidase from Arthrobacter globiformis (AGAO) is reversibly inhibited by molecular wires comprising a Ru(II) complex head group and an aromatic tail group joined by an alkane linker. The crystal structures of a series of Ru(II)-wire−AGAO complexes differing with respect to the length of the alkane linker have been determined. All wires lie in the AGAO active-site channel, with their aromatic tail group in contact with the trihydroxyphenylalanine quinone (TPQ) cofactor of the enzyme. The TPQ cofactor is consistently in its active (“off-Cu”) conformation, and the side chain of the so-called “gate” residue Tyr296 is consistently in the “gate-open” conformation. Among the wires tested, the most stable complex is produced when the wire has a −(CH_2)_4− linker. In this complex, the Ru(II)(phen)(bpy)_2 head group is level with the protein molecular surface. Crystal structures of AGAO in complex with optically pure forms of the C4 wire show that the linker and head group in the two enantiomers occupy slightly different positions in the active-site channel. Both the Λ and Δ isomers are effective competitive inhibitors of amine oxidation. Remarkably, inhibition by the C4 wire shows a high degree of selectivity for AGAO in comparison with other copper-containing amine oxidases.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja801289fDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja801289fPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja801289fPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518534PubMed CentralArticle
ORCID:
AuthorORCID
Gray, Harry B.0000-0002-7937-7876
Additional Information:© 2008 American Chemical Society. Received February 26, 2008. Publication Date (Web): May 29, 2008. We thank Nick Halpern-Manners and Alexander Dunn for assistance in the early stages of this work. The work was supported by the National Institutes of Health (DK19038 to H.B.G, GM27659 to D.M.D.) and the Australian Research Council (DP0208320 to J.M.G. and H.C.F.).
Funders:
Funding AgencyGrant Number
NIHDK19038
NIHGM27659
Australian Research CouncilDP0208320
Issue or Number:25
PubMed Central ID:PMC2518534
Record Number:CaltechAUTHORS:20170510-090742106
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170510-090742106
Official Citation:Enantiomer-Specific Binding of Ruthenium(II) Molecular Wires by the Amine Oxidase of Arthrobacter globiformis David B. Langley, Doreen E. Brown, Lionel E. Cheruzel, Stephen M. Contakes, Anthony P. Duff, Kimberly M. Hilmer, David M. Dooley, Harry B. Gray, J. Mitchell Guss, and Hans C. Freeman Journal of the American Chemical Society 2008 130 (25), 8069-8078 DOI: 10.1021/ja801289f
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:77331
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 May 2017 20:46
Last Modified:22 Nov 2019 09:58

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