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A well-balanced preexisting equilibrium governs electron flux efficiency of a multidomain diflavin reductase.

ABSTRACT: Diflavin reductases are bidomain electron transfer proteins in which structural reorientation is necessary to account for the various intramolecular and intermolecular electron transfer steps. Using small-angle x-ray scattering and nuclear magnetic resonance data, we describe the conformational free-energy landscape of the NADPH-cytochrome P450 reductase (CPR), a typical bidomain redox enzyme composed of two covalently-bound flavin domains, under various experimental conditions. The CPR enzyme exists in a salt- and pH-dependent rapid equilibrium between a previously described rigid, locked state and a newly characterized, highly flexible, unlocked state. We further establish that maximal electron flux through CPR is conditioned by adjustable stability of the locked-state domain interface under resting conditions. This is rationalized by a kinetic scheme coupling rapid conformational sampling and slow chemical reaction rates. Regulated domain interface stability associated with fast stochastic domain contacts during the catalytic cycle thus provides, to our knowledge, a new paradigm for improving our understanding of multidomain enzyme function.

SUBMITTER: Frances O

PROVIDER: S-EPMC4375552 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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A well-balanced preexisting equilibrium governs electron flux efficiency of a multidomain diflavin reductase.

Frances Oriane O Fatemi Fataneh F Pompon Denis D Guittet Eric E Sizun Christina C Pérez Javier J Lescop Ewen E Truan Gilles G

Biophysical journal 20150301 6

Diflavin reductases are bidomain electron transfer proteins in which structural reorientation is necessary to account for the various intramolecular and intermolecular electron transfer steps. Using small-angle x-ray scattering and nuclear magnetic resonance data, we describe the conformational free-energy landscape of the NADPH-cytochrome P450 reductase (CPR), a typical bidomain redox enzyme composed of two covalently-bound flavin domains, under various experimental conditions. The CPR enzyme e ...[more]

PMID: 25809265

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Dataset Information

A well-balanced preexisting equilibrium governs electron flux efficiency of a multidomain diflavin reductase.

Publications

A well-balanced preexisting equilibrium governs electron flux efficiency of a multidomain diflavin reductase.

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