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Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD
A covalently bound flavin cofactor is predominant in the succinate‐ubiquinone oxidoreductase (SQR; Complex II), an essential component of aerobic electron transport, and in the menaquinol‐fumarate oxidoreductase (QFR), the anaerobic counterpart, although it is only present in approximately 10 % of t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969107/ https://www.ncbi.nlm.nih.gov/pubmed/29124817 http://dx.doi.org/10.1002/chem.201704622 |
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author | Dourado, Daniel F. A. R. Swart, Marcel Carvalho, Alexandra T. P. |
author_facet | Dourado, Daniel F. A. R. Swart, Marcel Carvalho, Alexandra T. P. |
author_sort | Dourado, Daniel F. A. R. |
collection | PubMed |
description | A covalently bound flavin cofactor is predominant in the succinate‐ubiquinone oxidoreductase (SQR; Complex II), an essential component of aerobic electron transport, and in the menaquinol‐fumarate oxidoreductase (QFR), the anaerobic counterpart, although it is only present in approximately 10 % of the known flavoenzymes. This work investigates the role of this 8α‐N3‐histidyl linkage between the flavin adenine dinucleotide (FAD) cofactor and the respiratory Complex II. After parameterization with DFT calculations, classical molecular‐dynamics simulations and quantum‐mechanics calculations for Complex II:FAD and Complex II:FADH(2), with and without the covalent bond, were performed. It was observed that the covalent bond is essential for the active‐center arrangement of the FADH(2)/FAD cofactor. Removal of this bond causes a displacement of the isoalloxazine group, which influences interactions with the protein, flavin solvation, and possible proton‐transfer pathways. Specifically, for the noncovalently bound FADH(2) cofactor, the N1 atom moves away from the His‐A365 and His‐A254 residues and the N5 atom moves away from the glutamine‐62A residue. Both of the histidine and glutamine residues interact with a chain of water molecules that cross the enzyme, which is most likely involved in proton transfer. Breaking this chain of water molecules could thereby compromise proton transfer across the two active sites of Complex II. |
format | Online Article Text |
id | pubmed-5969107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59691072018-05-30 Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD Dourado, Daniel F. A. R. Swart, Marcel Carvalho, Alexandra T. P. Chemistry Full Papers A covalently bound flavin cofactor is predominant in the succinate‐ubiquinone oxidoreductase (SQR; Complex II), an essential component of aerobic electron transport, and in the menaquinol‐fumarate oxidoreductase (QFR), the anaerobic counterpart, although it is only present in approximately 10 % of the known flavoenzymes. This work investigates the role of this 8α‐N3‐histidyl linkage between the flavin adenine dinucleotide (FAD) cofactor and the respiratory Complex II. After parameterization with DFT calculations, classical molecular‐dynamics simulations and quantum‐mechanics calculations for Complex II:FAD and Complex II:FADH(2), with and without the covalent bond, were performed. It was observed that the covalent bond is essential for the active‐center arrangement of the FADH(2)/FAD cofactor. Removal of this bond causes a displacement of the isoalloxazine group, which influences interactions with the protein, flavin solvation, and possible proton‐transfer pathways. Specifically, for the noncovalently bound FADH(2) cofactor, the N1 atom moves away from the His‐A365 and His‐A254 residues and the N5 atom moves away from the glutamine‐62A residue. Both of the histidine and glutamine residues interact with a chain of water molecules that cross the enzyme, which is most likely involved in proton transfer. Breaking this chain of water molecules could thereby compromise proton transfer across the two active sites of Complex II. John Wiley and Sons Inc. 2017-12-14 2018-04-06 /pmc/articles/PMC5969107/ /pubmed/29124817 http://dx.doi.org/10.1002/chem.201704622 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Full Papers Dourado, Daniel F. A. R. Swart, Marcel Carvalho, Alexandra T. P. Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title | Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title_full | Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title_fullStr | Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title_full_unstemmed | Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title_short | Why the Flavin Adenine Dinucleotide (FAD) Cofactor Needs To Be Covalently Linked to Complex II of the Electron‐Transport Chain for the Conversion of FADH(2) into FAD |
title_sort | why the flavin adenine dinucleotide (fad) cofactor needs to be covalently linked to complex ii of the electron‐transport chain for the conversion of fadh(2) into fad |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969107/ https://www.ncbi.nlm.nih.gov/pubmed/29124817 http://dx.doi.org/10.1002/chem.201704622 |
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