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      Computational Identification and Analysis of Ubiquinone-Binding Proteins

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          Abstract

          Ubiquinone is an important cofactor that plays vital and diverse roles in many biological processes. Ubiquinone-binding proteins (UBPs) are receptor proteins that dock with ubiquinones. Analyzing and identifying UBPs via a computational approach will provide insights into the pathways associated with ubiquinones. In this work, we were the first to propose a UBPs predictor (UBPs-Pred). The optimal feature subset selected from three categories of sequence-derived features was fed into the extreme gradient boosting (XGBoost) classifier, and the parameters of XGBoost were tuned by multi-objective particle swarm optimization (MOPSO). The experimental results over the independent validation demonstrated considerable prediction performance with a Matthews correlation coefficient (MCC) of 0.517. After that, we analyzed the UBPs using bioinformatics methods, including the statistics of the binding domain motifs and protein distribution, as well as an enrichment analysis of the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.

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          Most cited references40

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          Architecture of succinate dehydrogenase and reactive oxygen species generation.

          The structure of Escherichia coli succinate dehydrogenase (SQR), analogous to the mitochondrial respiratory complex II, has been determined, revealing the electron transport pathway from the electron donor, succinate, to the terminal electron acceptor, ubiquinone. It was found that the SQR redox centers are arranged in a manner that aids the prevention of reactive oxygen species (ROS) formation at the flavin adenine dinucleotide. This is likely to be the main reason SQR is expressed during aerobic respiration rather than the related enzyme fumarate reductase, which produces high levels of ROS. Furthermore, symptoms of genetic disorders associated with mitochondrial SQR mutations may be a result of ROS formation resulting from impaired electron transport in the enzyme.
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            Crystal structure of mitochondrial respiratory membrane protein complex II.

            The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.
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              Biochemical functions of coenzyme Q10.

              F. Crane (2001)
              Coenzyme Q is well defined as a crucial component of the oxidative phosphorylation process in mitochondria which converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis. New roles for coenzyme Q in other cellular functions are only becoming recognized. The new aspects have developed from the recognition that coenzyme Q can undergo oxidation/reduction reactions in other cell membranes such as lysosomes. Golgi or plasma membranes. In mitochondria and lysosomes, coenzyme Q undergoes reduction/oxidation cycles during which it transfers protons across the membrane to form a proton gradient. The presence of high concentrations of quinol in all membranes provides a basis for antioxidant action either by direct reaction with radicals or by regeneration of tocopherol and ascorbate. Evidence for a function in redox control of cell signaling and gene expression is developing from studies on coenzyme Q stimulation of cell growth, inhibition of apoptosis, control of thiol groups, formation of hydrogen peroxide and control of membrane channels. Deficiency of coenzyme Q has been described based on failure of biosynthesis caused by gene mutation, inhibition of biosynthesis by HMG coA reductase inhibitors (statins) or for unknown reasons in ageing and cancer. Correction of deficiency requires supplementation with higher levels of coenzyme Q than are available in the diet.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                24 February 2020
                February 2020
                : 9
                : 2
                : 520
                Affiliations
                [1 ]School of Information Science and Technology, Northeast Normal University, Changchun 130117, China; luchang404@ 123456hotmail.com (C.L.); Jiangwj057@ 123456nenu.edu.cn (W.J.); wangh013@ 123456nenu.edu.cn (H.W.); jiangjx551@ 123456nenu.edu.cn (J.J.)
                [2 ]Institute of Computational Biology, Northeast Normal University, Changchun 130117, China
                [3 ]Department of Computer Science, College of Humanities & Sciences of Northeast Normal University, Changchun 130117, China
                Author notes
                Author information
                https://orcid.org/0000-0001-6331-622X
                https://orcid.org/0000-0002-4302-1886
                Article
                cells-09-00520
                10.3390/cells9020520
                7072731
                32102444
                7f04a669-3be2-4baa-b5dd-f57f2a488af9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 January 2020
                : 21 February 2020
                Categories
                Article

                ubiquinone-binding proteins,xgboost,binding domain motifs,gene ontology,kegg pathway

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