Significantly shorter Fe-S bond in cytochrome P450-I is consistent with greater reactivity relative to chloroperoxidase.
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.
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Courtney M
CM
Krest
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Alexey
A
Silakov
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Jonathan
J
Rittle
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Timothy H
TH
Yosca
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Elizabeth L
EL
Onderko
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Julio C
JC
Calixto
Department of Chemistry, Penn State University, University Park, Park, Pennsylvania 16802, USA.
Michael T
MT
Green
D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry; D002711:Chloride Peroxidase / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005658:Fungi / Q000201:enzymology; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D015204:Spectroscopy, Mossbauer; D016945:Sulfolobus acidocaldarius / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry*; D013696:Temperature
D019843:Archaeal Proteins; D011994:Recombinant Proteins; D013455:Sulfur; D002244:Carbon; D006859:Hydrogen; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D002711:Chloride Peroxidase; C408874:CYP119 protein, Sulfolobus solfataricus