1qmq: Difference between revisions
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==Overview== | ==Overview== | ||
The ability to detect, characterize, and manipulate specific biomolecules | The ability to detect, characterize, and manipulate specific biomolecules in complex media is critical for understanding metabolic processes. Particularly important targets are oxygenases (cytochromes P450) involved in drug metabolism and many disease states, including liver and kidney dysfunction, neurological disorders, and cancer. We have found that Ru photosensitizers linked to P450 substrates specifically recognize submicromolar cytochrome P450(cam) in the presence of other heme proteins. In the P450:Ru-substrate conjugates, energy transfer to the heme dramatically accelerates the Ru-luminescence decay. The crystal structure of a P450(cam):Ru-adamantyl complex reveals access to the active center via a channel whose depth (Ru-Fe distance is 21 A) is virtually the same as that extracted from an analysis of the energy-transfer kinetics. Suitably constructed libraries of sensitizer-linked substrates could be employed to probe the steric and electronic properties of buried active sites. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Pseudomonas putida]] | [[Category: Pseudomonas putida]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Crane, B | [[Category: Crane, B R.]] | ||
[[Category: Dmochowski, I | [[Category: Dmochowski, I J.]] | ||
[[Category: Gray, H | [[Category: Gray, H B.]] | ||
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: HEM]] | [[Category: HEM]] | ||
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[[Category: ru-substrate]] | [[Category: ru-substrate]] | ||
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Revision as of 15:41, 21 February 2008
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OPTICAL DETECTION OF CYTOCHROME P450 BY SENSITIZER-LINKED SUBSTRATES
OverviewOverview
The ability to detect, characterize, and manipulate specific biomolecules in complex media is critical for understanding metabolic processes. Particularly important targets are oxygenases (cytochromes P450) involved in drug metabolism and many disease states, including liver and kidney dysfunction, neurological disorders, and cancer. We have found that Ru photosensitizers linked to P450 substrates specifically recognize submicromolar cytochrome P450(cam) in the presence of other heme proteins. In the P450:Ru-substrate conjugates, energy transfer to the heme dramatically accelerates the Ru-luminescence decay. The crystal structure of a P450(cam):Ru-adamantyl complex reveals access to the active center via a channel whose depth (Ru-Fe distance is 21 A) is virtually the same as that extracted from an analysis of the energy-transfer kinetics. Suitably constructed libraries of sensitizer-linked substrates could be employed to probe the steric and electronic properties of buried active sites.
About this StructureAbout this Structure
1QMQ is a Single protein structure of sequence from Pseudomonas putida with , and as ligands. Active as Camphor 5-monooxygenase, with EC number 1.14.15.1 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Optical detection of cytochrome P450 by sensitizer-linked substrates., Dmochowski IJ, Crane BR, Wilker JJ, Winkler JR, Gray HB, Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):12987-90. PMID:10557259
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