Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase
Membrane cytochrome <i>b</i><sub>5</sub> reductase is a pleiotropic oxidoreductase that uses primarily soluble reduced nicotinamide adenine dinucleotide (NADH) as an electron donor to reduce multiple biological acceptors localized in cellular membranes. Some of the biological...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/1/118 |
| _version_ | 1797498915365322752 |
|---|---|
| author | Carlos Gutiérrez-Merino Oscar H. Martínez-Costa Maria Monsalve Alejandro K. Samhan-Arias |
| author_facet | Carlos Gutiérrez-Merino Oscar H. Martínez-Costa Maria Monsalve Alejandro K. Samhan-Arias |
| author_sort | Carlos Gutiérrez-Merino |
| collection | DOAJ |
| description | Membrane cytochrome <i>b</i><sub>5</sub> reductase is a pleiotropic oxidoreductase that uses primarily soluble reduced nicotinamide adenine dinucleotide (NADH) as an electron donor to reduce multiple biological acceptors localized in cellular membranes. Some of the biological acceptors of the reductase and coupled redox proteins might eventually transfer electrons to oxygen to form reactive oxygen species. Additionally, an inefficient electron transfer to redox acceptors can lead to electron uncoupling and superoxide anion formation by the reductase. Many efforts have been made to characterize the involved catalytic domains in the electron transfer from the reduced flavoprotein to its electron acceptors, such as cytochrome <i>b</i><sub>5</sub>, through a detailed description of the flavin and NADH-binding sites. This information might help to understand better the processes and modifications involved in reactive oxygen formation by the cytochrome <i>b</i><sub>5</sub> reductase. Nevertheless, more than half a century since this enzyme was first purified, the one-electron transfer process toward potential electron acceptors of the reductase is still only partially understood. New advances in computational analysis of protein structures allow predicting the intramolecular protein dynamics, identifying potential functional sites, or evaluating the effects of microenvironment changes in protein structure and dynamics. We applied this approach to characterize further the roles of amino acid domains within cytochrome <i>b</i><sub>5</sub> reductase structure, part of the catalytic domain, and several sensors and structural domains involved in the interactions with cytochrome <i>b</i><sub>5</sub> and other electron acceptors. The computational analysis results allowed us to rationalize some of the available spectroscopic data regarding ligand-induced conformational changes leading to an increase in the flavin adenine dinucleotide (FAD) solvent-exposed surface, which has been previously correlated with the formation of complexes with electron acceptors. |
| first_indexed | 2024-03-10T03:41:01Z |
| format | Article |
| id | doaj.art-e9cbb6968d97456e8c0dc4e6173b45ac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:41:01Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e9cbb6968d97456e8c0dc4e6173b45ac2023-11-23T11:35:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123111810.3390/ijms23010118Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> ReductaseCarlos Gutiérrez-Merino0Oscar H. Martínez-Costa1Maria Monsalve2Alejandro K. Samhan-Arias3Department of Biochemistry and Molecular Biology, Faculty of Sciences and Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, Av. Elvas S/N, 06006 Badajoz, SpainInstituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, SpainInstituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, SpainInstituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), Arturo Duperier, 4, 28029 Madrid, SpainMembrane cytochrome <i>b</i><sub>5</sub> reductase is a pleiotropic oxidoreductase that uses primarily soluble reduced nicotinamide adenine dinucleotide (NADH) as an electron donor to reduce multiple biological acceptors localized in cellular membranes. Some of the biological acceptors of the reductase and coupled redox proteins might eventually transfer electrons to oxygen to form reactive oxygen species. Additionally, an inefficient electron transfer to redox acceptors can lead to electron uncoupling and superoxide anion formation by the reductase. Many efforts have been made to characterize the involved catalytic domains in the electron transfer from the reduced flavoprotein to its electron acceptors, such as cytochrome <i>b</i><sub>5</sub>, through a detailed description of the flavin and NADH-binding sites. This information might help to understand better the processes and modifications involved in reactive oxygen formation by the cytochrome <i>b</i><sub>5</sub> reductase. Nevertheless, more than half a century since this enzyme was first purified, the one-electron transfer process toward potential electron acceptors of the reductase is still only partially understood. New advances in computational analysis of protein structures allow predicting the intramolecular protein dynamics, identifying potential functional sites, or evaluating the effects of microenvironment changes in protein structure and dynamics. We applied this approach to characterize further the roles of amino acid domains within cytochrome <i>b</i><sub>5</sub> reductase structure, part of the catalytic domain, and several sensors and structural domains involved in the interactions with cytochrome <i>b</i><sub>5</sub> and other electron acceptors. The computational analysis results allowed us to rationalize some of the available spectroscopic data regarding ligand-induced conformational changes leading to an increase in the flavin adenine dinucleotide (FAD) solvent-exposed surface, which has been previously correlated with the formation of complexes with electron acceptors.https://www.mdpi.com/1422-0067/23/1/118cytochrome <i>b</i><sub>5</sub> reductasecytochrome <i>b</i><sub>5</sub>superoxide anion radicalelectron transferprotein intrinsic dynamics |
| spellingShingle | Carlos Gutiérrez-Merino Oscar H. Martínez-Costa Maria Monsalve Alejandro K. Samhan-Arias Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase International Journal of Molecular Sciences cytochrome <i>b</i><sub>5</sub> reductase cytochrome <i>b</i><sub>5</sub> superoxide anion radical electron transfer protein intrinsic dynamics |
| title | Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase |
| title_full | Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase |
| title_fullStr | Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase |
| title_full_unstemmed | Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase |
| title_short | Structural Features of Cytochrome <i>b</i><sub>5</sub>–Cytochrome <i>b</i><sub>5</sub> Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome <i>b</i><sub>5</sub> Reductase |
| title_sort | structural features of cytochrome i b i sub 5 sub cytochrome i b i sub 5 sub reductase complex formation and implications for the intramolecular dynamics of cytochrome i b i sub 5 sub reductase |
| topic | cytochrome <i>b</i><sub>5</sub> reductase cytochrome <i>b</i><sub>5</sub> superoxide anion radical electron transfer protein intrinsic dynamics |
| url | https://www.mdpi.com/1422-0067/23/1/118 |
| work_keys_str_mv | AT carlosgutierrezmerino structuralfeaturesofcytochromeibisub5subcytochromeibisub5subreductasecomplexformationandimplicationsfortheintramoleculardynamicsofcytochromeibisub5subreductase AT oscarhmartinezcosta structuralfeaturesofcytochromeibisub5subcytochromeibisub5subreductasecomplexformationandimplicationsfortheintramoleculardynamicsofcytochromeibisub5subreductase AT mariamonsalve structuralfeaturesofcytochromeibisub5subcytochromeibisub5subreductasecomplexformationandimplicationsfortheintramoleculardynamicsofcytochromeibisub5subreductase AT alejandroksamhanarias structuralfeaturesofcytochromeibisub5subcytochromeibisub5subreductasecomplexformationandimplicationsfortheintramoleculardynamicsofcytochromeibisub5subreductase |