ArticleThe FEBS journal2014
Distinct conformational behaviors of four mammalian dual-flavin reductases (cytochrome P450 reductase, methionine synthase reductase, neuronal nitric oxide synthase, endothelial nitric oxide synthase) determine their unique catalytic profiles.
Article in The FEBS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Enzymatic and Biophysical Analysis of two Highly Related Cytochrome P450 Reductases frombioRxiv : the preprint server for biology · 2026Article
- Structural insights into cobalamin loading and reactivation of human methionine synthase.Nature communications · 2026Article
- Probing calmodulin-NO synthase interactions via site-specific infrared spectroscopy: an introductory investigation.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- Confrontation of AlphaFold models with experimental structures enlightens conformational dynamics supporting CYP102A1 functions.Scientific reports · 2022Article
- Conformational states and fluctuations in endothelial nitric oxide synthase under calmodulin regulation.Biophysical journal · 2021Article
- Cryo-EM reveals the architecture of the dimeric cytochrome P450 CYP102A1 enzyme and conformational changes required for redox partner recognition.The Journal of biological chemistry · 2020Article
- Nitric oxide synthase enzymology in the 20 years after the Nobel Prize.British journal of pharmacology · 2019Review
- Exploring the conformations of nitric oxide synthase with fluorescence.Frontiers in bioscience (Landmark edition) · 2018Review
- Deciphering mechanism of conformationally controlled electron transfer in nitric oxide synthases.Frontiers in bioscience (Landmark edition) · 2018Review
- Direct observation of multiple conformational states in Cytochrome P450 oxidoreductase and their modulation by membrane environment and ionic strength.Scientific reports · 2018Article
- Solution structure of the cytochrome P450 reductase-cytochromeThe Journal of biological chemistry · 2018Article
- Article
- Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase.Scientific reports · 2017Article
- Restricting the conformational freedom of the neuronal nitric-oxide synthase flavoprotein domain reveals impact on electron transfer and catalysis.The Journal of biological chemistry · 2017Article
- The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength.Frontiers in pharmacology · 2017Article
- Phosphorylation Controls Endothelial Nitric-oxide Synthase by Regulating Its Conformational Dynamics.The Journal of biological chemistry · 2016Article
- Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study.Journal of inorganic biochemistry · 2015Article
- Real-time analysis of conformational control in electron transfer reactions of human cytochrome P450 reductase with cytochrome c.The FEBS journal · 2015Article
- Single-molecule spectroscopy reveals how calmodulin activates NO synthase by controlling its conformational fluctuation dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Multidomain enzymes often rely on large conformational motions to function. However, the conformational setpoints, rates of domain motions and relationships between these parameters and catalytic activity are not well understood. To address this, we determined and compared the conformational setpoints and the rates of conformational switching between closed unreactive and open reactive states in four mammalian diflavin NADPH oxidoreductases that catalyze important biological electron transfer reactions: cytochrome P450 reductase, methionine synthase reductase and endothelial and neuronal nitric oxide synthase. We used stopped-flow spectroscopy, single turnover methods and a kinetic model that relates electron flux through each enzyme to its conformational setpoint and its rates of conformational switching. The results show that the four flavoproteins, when fully-reduced, have a broad range of conformational setpoints (from 12% to 72% open state) and also vary 100-fold with respect to their rates of conformational switching between unreactive closed and reactive open states (cytochrome P450 reductase > neuronal nitric oxide synthase > methionine synthase reductase > endothelial nitric oxide synthase). Furthermore, simulations of the kinetic model could explain how each flavoprotein can support its given rate of electron flux (cytochrome c reductase activity) based on its unique conformational setpoint and switching rates. The present study is the first to quantify these conformational parameters among the diflavin enzymes and suggests how the parameters might be manipulated to speed or slow biological electron flux.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.