What question did this study set out to answer?

Determine the molecular recognition mechanisms in cytochrome P-450 active sites that govern partitioning across catalytic branch points during substrate hydroxylation versus uncoupling pathways.

January 1, 1993Biochemistry

Molecular recognition in cytochrome P-450: Mechanism for the control of uncoupling reactions

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PLPaul J. LoidaMonsanto (United States)SSStephen G. SligarMarquette University

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Implication

In vitro mutational study reveals active-site topology controls uncoupling branch points in cytochrome P450 monooxygenases, indicating pocket hydration dictates hydrogen peroxide release.

Key Points

Determine the molecular recognition mechanisms in cytochrome P-450 active sites that govern partitioning across catalytic branch points during substrate hydroxylation versus uncoupling pathways.
Engineered site-directed active-site mutations in cytochrome P-450 designed to alter binding pocket topology during ethylbenzene hydroxylation.
Quantified the recovery of NADH-derived reducing equivalents across three partitioned products: hydroxylated substrate, hydrogen peroxide, and water.
Direct release of superoxide at the first branch point failed to compete with the second electron transfer step across all evaluated substrates.
Alterations in active-site topology shifted reaction specificity at both the second branch point (peroxide release) and the third branch point (water formation).
Mutants exhibited increased catalytic commitment, with hydrogen peroxide generation showing no correlation to mutation coordinates within the pocket, implicating active-site hydration in uncoupling control.

Cite This Study

Loida et al. (1993) studied this question.

synapsesocial.com/papers/6a7ec6c0769bdd359bcda1ed https://doi.org/10.1021/bi00094a009

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Implication

In vitro mutational study reveals active-site topology controls uncoupling branch points in cytochrome P450 monooxygenases, indicating pocket hydration dictates hydrogen peroxide release.

Molecular recognition in cytochrome P-450: Mechanism for the control of uncoupling reactions

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Implication

Key Points

Cite This Study

Molecular recognition in cytochrome P-450: Mechanism for the control of uncoupling reactions

Discussion

Member takes

Implication

Key Points

Cite This Study

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