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Fluorescent probes for cytochrome p450 structural characterization and inhibitor screening

Academic Article
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Overview

authors

  • Dunn, A. R.
  • Hays, A. M. A.
  • Goodin, D. B.
  • Stout, C. David
  • Chiu, R.
  • Winkler, J. R.
  • Gray, H. B.

publication date

  • September 2002

journal

  • Journal of the American Chemical Society  Journal

abstract

  • We have synthesized two luminescent probes (D-4-Ad and D-8-Ad) that target cytochrome P450cam. D-4-Ad luminescence is quenched by Förster energy transfer upon binding (Kd = 0.83 muM) but is restored when the probe is displaced from the active site by camphor. In contrast, D-8-Ad (Kd approximately 0.02 muM) is not displaced from the enzyme, even in the presence of a large excess of camphor. The 2.2 A resolution crystal structure of the D-8-Ad:P450cam complex reveals extensive hydrophobic contacts between the probe and the enzyme, which result from the conformational flexibility of the B', F, and G helices. Probes with properties similar to those of D-4-Ad potentially could be useful for screening P450 inhibitors.

subject areas

  • Adamantane
  • Binding, Competitive
  • Camphor
  • Camphor 5-Monooxygenase
  • Dansyl Compounds
  • Fluorescent Dyes
  • Kinetics
  • Models, Molecular
  • Spectrometry, Fluorescence
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja0271678

PubMed ID

  • 12197708
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Additional Document Info

start page

  • 10254

end page

  • 10255

volume

  • 124

issue

  • 35

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