Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.H...Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.However,studies in this field are limited by the difficulty in experimentally identifying the substrate site specificity of lysine succinylation.To facilitate this process,several tools have been proposed for the computational identification of succinylated lysine sites.In this study,we developed an approach to investigate the substrate specificity of lysine succinylated sites based on amino acid composition.Using experimentally verified lysine succinylated sites collected from public resources,the significant differences in position-specific amino acid composition between succinylated and non-succinylated sites were represented using the Two Sample Logo program.These findings enabled the adoption of an effective machine learning method,support vector machine,to train a predictive model with not only the amino acid composition,but also the composition of k-spaced amino acid pairs.After the selection of the best model using a ten-fold crossvalidation approach,the selected model significantly outperformed existing tools based on an independent dataset manually extracted from published research articles.Finally,the selected model was used to develop a web-based tool,SuccSite,to aid the study of protein succinylation.Two proteins were used as case studies on the website to demonstrate the effective prediction of succinylation sites.We will regularly update SuccSite by integrating more experimental datasets.SuccSite is freely accessible at http://csb.cse.yzu.edu.tw/SuccSite/.展开更多
Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic...Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic,and evolutionarily conserved^4 where it has been comprehensively studied in both bacterial and mammalian cells^5-7.Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated^5-7.Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases,including cardiovascular diseases and cancer^7-9.Therefore,an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases.In this review,we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.展开更多
Low molecular weight N-succinyl-chitosans with different degrees of substitution were synthesized by controlling reaction temperature, reaction time, and the molar ratio of the low molecular weight chitosan to succini...Low molecular weight N-succinyl-chitosans with different degrees of substitution were synthesized by controlling reaction temperature, reaction time, and the molar ratio of the low molecular weight chitosan to succinic anhydride. The structure of the low molecular weight N-succinyl-chitosan was characterized by infrared spectroscopy(IR), by which —COCH_ 2CH_ 2COOH was proved to be introduced to the —NH_ 2 of the low molecular weight chitosan. The moisture adsorption and moisture retention capacities of the low molecular weight chitosan derivatives with different degrees of substitution were investigated. The results indicate that the moisture adsorption and moisture retention capacities of the low molecular weight N-succinyl-chitosan increase with the increase of the degree of substitution. When the degree of substitution is greater than 38%, the derivatives have better moisture adsorption and moisture retention capacities than hyaluronic acid.展开更多
基金the Warshel Institute for Computational Biology,School of Life and Health Sciences,The Chinese University of Hong Kong,Shenzhen,China for financially supporting this research
文摘Protein succinylation is a biochemical reaction in which a succinyl group(-CO-CH2-CH2-CO-)is attached to the lysine residue of a protein molecule.Lysine succinylation plays important regulatory roles in living cells.However,studies in this field are limited by the difficulty in experimentally identifying the substrate site specificity of lysine succinylation.To facilitate this process,several tools have been proposed for the computational identification of succinylated lysine sites.In this study,we developed an approach to investigate the substrate specificity of lysine succinylated sites based on amino acid composition.Using experimentally verified lysine succinylated sites collected from public resources,the significant differences in position-specific amino acid composition between succinylated and non-succinylated sites were represented using the Two Sample Logo program.These findings enabled the adoption of an effective machine learning method,support vector machine,to train a predictive model with not only the amino acid composition,but also the composition of k-spaced amino acid pairs.After the selection of the best model using a ten-fold crossvalidation approach,the selected model significantly outperformed existing tools based on an independent dataset manually extracted from published research articles.Finally,the selected model was used to develop a web-based tool,SuccSite,to aid the study of protein succinylation.Two proteins were used as case studies on the website to demonstrate the effective prediction of succinylation sites.We will regularly update SuccSite by integrating more experimental datasets.SuccSite is freely accessible at http://csb.cse.yzu.edu.tw/SuccSite/.
基金We apologize to any authors whose work could not be included owing to space limitations.This work was supported in part by NIH R01 CA225680-01(T.H.)Research Scholar Grant(RSG-19-076-01-TBE)from the American Cancer Society(T.H.)Career Catalyst Research funding(CCR14300798)from the Susan G.Komen Foundation(T.H.),the Eagles Cancer Research Fund(T.H.),a Team Science Platform Award from the Mayo Clinic Center for Biomedical Discovery(T.H.),the Developmental Therapeutics Program from the Mayo Clinic Cancer Center(T.H.),and the Mayo Clinic Breast SPORE P50CA 116201-10(T.H.).E.K.W.was supported by a predoctoral fellowship from the Mayo Foundation for Education and Research.
文摘Lysine succinylation(Ksucc),defined as a transfer of a succinyl group to a lysine residue of a protein,is a newly identified protein post-translational modification^1-3.This chemical modification is reversible,dynamic,and evolutionarily conserved^4 where it has been comprehensively studied in both bacterial and mammalian cells^5-7.Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated^5-7.Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases,including cardiovascular diseases and cancer^7-9.Therefore,an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases.In this review,we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.
文摘Low molecular weight N-succinyl-chitosans with different degrees of substitution were synthesized by controlling reaction temperature, reaction time, and the molar ratio of the low molecular weight chitosan to succinic anhydride. The structure of the low molecular weight N-succinyl-chitosan was characterized by infrared spectroscopy(IR), by which —COCH_ 2CH_ 2COOH was proved to be introduced to the —NH_ 2 of the low molecular weight chitosan. The moisture adsorption and moisture retention capacities of the low molecular weight chitosan derivatives with different degrees of substitution were investigated. The results indicate that the moisture adsorption and moisture retention capacities of the low molecular weight N-succinyl-chitosan increase with the increase of the degree of substitution. When the degree of substitution is greater than 38%, the derivatives have better moisture adsorption and moisture retention capacities than hyaluronic acid.
