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

Courtney M. Krest, Alexey Silakov, Jonathan Rittle, Timothy H. Yosca, Elizabeth L. Onderko, Julio C. Calixto, Michael T. Green

Research output: Contribution to journalArticle

46 Citations (Scopus)

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. 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. This observation may in part explain P450's greater propensity for C-H bond activation.

Original languageEnglish (US)
Pages (from-to)696-702
Number of pages7
JournalNature Chemistry
Volume7
Issue number9
DOIs
StatePublished - Sep 22 2015

Fingerprint

Chloride Peroxidase
Cytochrome P-450 Enzyme System
Hydrogen bonds
Chemical activation
Ligands
X ray absorption spectroscopy
Bond length
Heme
Proteins
Carbon
Electrons
Temperature

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

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. In: Nature Chemistry. 2015 ; Vol. 7, No. 9. pp. 696-702.
@article{9abe287e97534ce5972b56dcad0b25e7,
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. To provide insight into the differing reactivities of these intermediates, we examined CPO-I and P450-I using variable-temperature M{\"o}ssbauer 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. This observation may in part explain P450's greater propensity for C-H bond activation.",
author = "Krest, {Courtney M.} and Alexey Silakov and Jonathan Rittle and Yosca, {Timothy H.} and Onderko, {Elizabeth L.} and Calixto, {Julio C.} and Green, {Michael T.}",
year = "2015",
month = "9",
day = "22",
doi = "10.1038/nchem.2306",
language = "English (US)",
volume = "7",
pages = "696--702",
journal = "Nature Chemistry",
issn = "1755-4330",
publisher = "Nature Publishing Group",
number = "9",

}

Significantly shorter Fe-S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase. / Krest, Courtney M.; Silakov, Alexey; Rittle, Jonathan; Yosca, Timothy H.; Onderko, Elizabeth L.; Calixto, Julio C.; Green, Michael T.

In: Nature Chemistry, Vol. 7, No. 9, 22.09.2015, p. 696-702.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Significantly shorter Fe-S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase

AU - Krest, Courtney M.

AU - Silakov, Alexey

AU - Rittle, Jonathan

AU - Yosca, Timothy H.

AU - Onderko, Elizabeth L.

AU - Calixto, Julio C.

AU - Green, Michael T.

PY - 2015/9/22

Y1 - 2015/9/22

N2 - 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. 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. This observation may in part explain P450's greater propensity for C-H bond activation.

AB - 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. 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. This observation may in part explain P450's greater propensity for C-H bond activation.

UR - http://www.scopus.com/inward/record.url?scp=84939799805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939799805&partnerID=8YFLogxK

U2 - 10.1038/nchem.2306

DO - 10.1038/nchem.2306

M3 - Article

C2 - 26291940

AN - SCOPUS:84939799805

VL - 7

SP - 696

EP - 702

JO - Nature Chemistry

JF - Nature Chemistry

SN - 1755-4330

IS - 9

ER -