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Title: Significantly shorter Fe–S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase

Abstract

Cytochrome P450 (P450) and chloroperoxidase (CPO) are thiolate-ligated haem proteins that catalyse the activation of carbon hydrogen bonds. The principal intermediate in these reactions is a ferryl radical species called compound I. P450 compound I (P450-I) is significantly more reactive than CPO-I, which only cleaves activated C–H bonds. In this paper, to provide insight into the differing reactivities of these intermediates, we examined CPO-I and P450-I using variable-temperature Mössbauer and X-ray absorption spectroscopies. These measurements indicate that the Fe–S bond is significantly shorter in P450-I than in CPO-I. This difference in Fe–S bond lengths can be understood in terms of variations in the hydrogen-bonding patterns within the ‘cys-pocket’ (a portion of the proximal helix that encircles the thiolate ligand). Weaker hydrogen bonding in P450-I results in a shorter Fe–S bond, which enables greater electron donation from the axial thiolate ligand. Finally, this observation may in part explain P450's greater propensity for C–H bond activation.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [2]
  1. SLAC National Accelerator Lab., Menlo Park, CA (United States); Pennsylvania State Univ., University Park, PA (United States)
  2. Pennsylvania State Univ., University Park, PA (United States)
Publication Date:
Research Org.:
Pennsylvania State Univ., University Park, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1347116
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
Nature Chemistry
Additional Journal Information:
Journal Volume: 7; Journal Issue: 9; Journal ID: ISSN 1755-4330
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; biocatalysis; metalloproteins

Citation Formats

Krest, Courtney M., Silakov, Alexey, Rittle, Jonathan, Yosca, Timothy H., Onderko, Elizabeth L., Calixto, Julio C., and Green, Michael T. Significantly shorter Fe–S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase. United States: N. p., 2015. Web. doi:10.1038/nchem.2306.
Krest, Courtney M., Silakov, Alexey, Rittle, Jonathan, Yosca, Timothy H., Onderko, Elizabeth L., Calixto, Julio C., & Green, Michael T. Significantly shorter Fe–S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase. United States. doi:10.1038/nchem.2306.
Krest, Courtney M., Silakov, Alexey, Rittle, Jonathan, Yosca, Timothy H., Onderko, Elizabeth L., Calixto, Julio C., and Green, Michael T. Mon . "Significantly shorter Fe–S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase". United States. doi:10.1038/nchem.2306. https://www.osti.gov/servlets/purl/1347116.
@article{osti_1347116,
title = {Significantly shorter Fe–S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase},
author = {Krest, Courtney M. and Silakov, Alexey and Rittle, Jonathan and Yosca, Timothy H. and Onderko, Elizabeth L. and Calixto, Julio C. and Green, Michael T.},
abstractNote = {Cytochrome P450 (P450) and chloroperoxidase (CPO) are thiolate-ligated haem proteins that catalyse the activation of carbon hydrogen bonds. The principal intermediate in these reactions is a ferryl radical species called compound I. P450 compound I (P450-I) is significantly more reactive than CPO-I, which only cleaves activated C–H bonds. In this paper, to provide insight into the differing reactivities of these intermediates, we examined CPO-I and P450-I using variable-temperature Mössbauer and X-ray absorption spectroscopies. These measurements indicate that the Fe–S bond is significantly shorter in P450-I than in CPO-I. This difference in Fe–S bond lengths can be understood in terms of variations in the hydrogen-bonding patterns within the ‘cys-pocket’ (a portion of the proximal helix that encircles the thiolate ligand). Weaker hydrogen bonding in P450-I results in a shorter Fe–S bond, which enables greater electron donation from the axial thiolate ligand. Finally, this observation may in part explain P450's greater propensity for C–H bond activation.},
doi = {10.1038/nchem.2306},
journal = {Nature Chemistry},
number = 9,
volume = 7,
place = {United States},
year = {2015},
month = {8}
}

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Cited by: 20 works
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