Regulation of ferryl reactivity by the cytochrome P450 decarboxylase OleT

被引:0
作者
Gering, Hannah E. [1 ]
Manley, Olivia M. [1 ]
Holwerda, Alexis J. [2 ]
Grant, Job L. [2 ]
Ratigan, Steven C. [2 ]
Makris, Thomas M. [1 ,3 ]
机构
[1] North Carolina State Univ, Dept Struct & Mol Biochem, 120 West Broughton Dr, Raleigh, NC 27607 USA
[2] Univ South Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA
[3] North Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
基金
美国国家科学基金会;
关键词
Cytochrome P450; Compound I; CYP152; HYDROGEN-ATOM TRANSFER; COUPLED ELECTRON-TRANSFER; ACID ALPHA-HYDROXYLASE; COMPOUND-I FORMATION; H BOND ACTIVATION; KINETIC CHARACTERIZATION; ALKANE HYDROXYLATION; P450; ENZYMES; MECHANISM; PEROXYGENASE;
D O I
10.1016/j.jinorgbio.2025.112912
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cytochrome P450 OleT catalyzes the decarboxylation of long-chain fatty acid substrates to produce terminal alkenes using hydrogen peroxide as a co-substrate. The facile activation of peroxide to form Compound I in the first step of the reaction, and subsequent C-C bond cleavage mediated by Compound II, provides a unique opportunity to visualize both ferryl intermediates using transient kinetic approaches. Analysis of the Arrhenius behavior yields activation barriers of similar to 6 kcal/mol and similar to 18 kcal/mol for the decay of Compound I and Compound II respectively. The influence of the secondary coordination sphere, probed through site-directed mutagenesis approaches, suggests that restriction of the donor-acceptor distance contributes to the reactivity of Compound I. The reactivity of Compound II was further probed using kinetic solvent isotope effect approaches, confirming that the large barrier owes to a proton-gated mechanism in the decarboxylation reaction coordinate. Hydrogen-bonding to an active-site histidine (H85) in the distal pocket plays a key role in this process.
引用
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页数:9
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