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Conjugates of Heme-Thiolate Enzymes with Photoactive Metal-Diimine Wires

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Photofunctional Transition Metal Complexes

Part of the book series: Structure and Bonding ((STRUCTURE,volume 123))

Abstract

Heme-thiolate enzymes, notably cytochromes P450 and nitric oxide synthases, use dioxygen to oxygenatesubstrates. Photoactive metal-diimine molecular wires that are capable of effecting rapid redox state changesat buried active sites have been developed to generate intermediates in the catalytic cycles of these enzymes.Wires that feature a photoactive head group tethered to an active-site ligand bind P450CAM and induciblenitric oxide synthase (iNOS) primarily by hydrophobic interactions. The wire-binding specificity of eachenzyme is critically dependent on the structural flexibility of the protein. P450CAM:wire conjugates canadopt open or partially open conformations, thereby accommodating a wide range of wires, whereas onlylong wires with smaller [Re(CO)3(bpy)Im]+ head groupsare able to bind tightly in the rigid active-site channel of iNOS. Dansyl-terminated molecular wires functionas highly sensitive and isoform specific fluorescent sensors for P450CAM.

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Abbreviations

Ad:

adamantyl

BH4 :

tetrahydrobiopterin

CPR:

cytochrome P450 reductase

EB:

ethylbenzene

eNOS:

endothelial nitric oxide synthase

ET:

electron transfer

FAD:

flavin adenosine dinucleotide

FET:

fluorescence energy transfer

FMN:

flavin mononucleotide

iNOS:

inducible nitric oxide synthase

iNOS oxy :

oxygenase domain of inducible NOS

NADPH:

nicotinamide adenosine dinucleotide hydride

NHE:

normal hydrogen electrode

nNOS:

neuronal nitric oxide synthase

NOS:

nitric oxide synthase

P450:

cytochrome P450

P450BM3:

cytochrome P450 from Bacillus megaterium

P450CAM:

cytochrome P450 from Pseudomonas putida

pdx:

putidaredoxin

tm:

tetramethyl

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Acknowledgments

Figure 11 was adopted from a version prepared by Alex Dunn. We thank him and others in the Caltech molecular wires group (Ivan Dmochowski, Jon Wilker, Corinna Hess, Wendy Belliston-Bittner, Nick Halpern-Manners) for contributions that are summarized in this chapter. Our work is supported by NIH, NSF, the Ellison Medical Foundation Senior Scholar Award in Aging (to HBG), and the Arnold and Mabel Beckman Foundation.

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Authors and Affiliations

  1. Beckman Institute, California Institute of Technology, 1200 E. California Blvd., 91125, Pasadena, CA, USA

    Stephen M. Contakes, Yen Hoang Le Nguyen & Harry B. Gray

  2. Department of Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., 92037, La Jolla, CA, USA

    Edith C. Glazer & David B. Goodin

  3. AMBRX, 10975 N. Torrey Pines Rd., 92037, La Jolla, CA, USA

    Anna-Maria Hays

Authors
  1. Stephen M. Contakes
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  2. Yen Hoang Le Nguyen
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  3. Harry B. Gray
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  4. Edith C. Glazer
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  5. Anna-Maria Hays
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  6. David B. Goodin
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Corresponding author

Correspondence to Harry B. Gray .

Editor information

Vivian W. W. Yam

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© 2006 Springer-Verlag Berlin Heidelberg

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Contakes, S.M., Nguyen, Y.H.L., Gray, H.B., Glazer, E.C., Hays, AM., Goodin, D.B. (2006). Conjugates of Heme-Thiolate Enzymes with Photoactive Metal-Diimine Wires. In: Yam, V.W.W. (eds) Photofunctional Transition Metal Complexes. Structure and Bonding, vol 123. Springer, Berlin, Heidelberg. https://doi.org/10.1007/430_2006_039

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