Iron(IV)hydroxide pKa and the Role of Thiolate Ligation in C-H Bond Activation by Cytochrome P450

The pKa of P450Cytochrome P450 enzymes oxidize hydrocarbons through activation of oxygen at heme iron centers. However, the protein backbone has various sites (particularly tyrosine residues) that are also sensitive to oxidation, so how can the enzyme rapidly transform substrates without attacking i...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-11, Vol.342 (6160), p.825-829
Main Authors: Yosca, Timothy H, Rittle, Jonathan, Krest, Courtney M, Onderko, Elizabeth L, Silakov, Alexey, Calixto, Julio C, Behan, Rachel K, Green, Michael T
Format: Article
Language:English
Subjects:
Activation
Backbone
Electronics
Enzymes
Iron
Residues
Substrates
Tyrosine
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Summary:The pKa of P450Cytochrome P450 enzymes oxidize hydrocarbons through activation of oxygen at heme iron centers. However, the protein backbone has various sites (particularly tyrosine residues) that are also sensitive to oxidation, so how can the enzyme rapidly transform substrates without attacking itself? Yosca et al. (p. 825) explored the energetics of the competition between substrate and self-oxidation by measuring the pKa of the enzyme's iron(IV)hydroxide motif. Cysteine thiolate coordination to iron in the P450 structure raised the pKa almost to 12-rendering the iron oxo far more basic than analogous motifs in other heme environments. Correspondingly, the electronic environment for H-atom transfer from the substrate was relatively favorable, compared to electron transfer from a backbone residue.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1244373