Natural protein channels have evolved with fantastic spatial structures,which play pivotal physiological functions in all living systems.Learning from nature,chemical scientists have developed a myriad of artificial t...Natural protein channels have evolved with fantastic spatial structures,which play pivotal physiological functions in all living systems.Learning from nature,chemical scientists have developed a myriad of artificial transmembrane ion channels by using various chemical strategies,among which the non-covalent supramolecular ion channels exhibit remarkable advantages over other forms(e.g.,single-molecule ion channel),which exhibited facile preparation methods,easier structural modification and functionalization.In this review,we have systematically summarized the recent progress of supramolecular self-assembled artificial transmembrane ion channels,which were classified by different self-assembly mechanisms,such as hydrogen bonds,π-πinteractions,etc.Detailed preparation process and self-assembly strategies of the supramolecular ion channels have been described.Moreover,potential biomedical applications of the supramolecular ion channels have also been carefully discussed in this review.Finally,future opportunities and challenges facing this field were also elaborately discussed.It is anticipated that this review could provide a panoramic sketch and future directions towards the construction of novel artificial ion channels with novel functions and biomedical applications.展开更多
Glutathione peroxidase (GPx, EC1.11.1.9), an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, thereby protecting cells and other biological issu...Glutathione peroxidase (GPx, EC1.11.1.9), an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, thereby protecting cells and other biological issues against oxidative damage. It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant. In order to de- velop a general strategy for specifically targeting and operating selenium in active sites of enzymes, the catalytically essential residue selenocysteine (Sec) was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system. The studies of the catalytic activity and the steady-state kinetics demonstrated that selenosubtilisin is an excellent GPx-like bio- catalyst. In comparison with the chemically modified method, biosynthesis exhibits obvious advan- tages: Sec could be site-directly incorporated into active sites of enzymes to overcome the non-speci- ficity generated by chemical modification. This study provides an important strategy for specifically targeting and operating selenium in the active site of an enzyme.展开更多
Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved duri...Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved during the processes catalyzed by enzymes. It is plausible that the entire macromolecular scaffold is involved in catalysis via cooperative motions that result in incredible catalytic efficiency. Moreover, some enzymes can very strongly bind the transition state with an association constant of up to 1024 M-1, suggesting that covalent bond formation is a possible process during the conversion of the transition state in enzyme catalysis, in addition to the concatenation of noncovalent interactions. Supramolecular chemistry provides fundamental knowledge about the relationships between the dynamic structures and functions of organized molecules. By tak-ing advantage of supramolecular concepts, numerous supramolecular enzyme mimics with complex and hierarchical structures have been designed and investigated. Through the study of supramolecular enzyme models, a great deal of information to aid our understanding of the mechanism of catalysis by natural enzymes has been acquired. With the development of supramolec-ular artificial enzymes, it is possible to replicate the features of natural enzymes with regards to their constitutional complexity and cooperative motions, and eventually decipher the conformation-based catalytic mystery of natural enzymes.展开更多
We have described the synthesis of a series of poly(aryl ether) dendrimers with telluride in the core and oligo(ethylene oxide) chains at the pe- riphery which act as glutathione peroxidase (GPx) mimics. These series ...We have described the synthesis of a series of poly(aryl ether) dendrimers with telluride in the core and oligo(ethylene oxide) chains at the pe- riphery which act as glutathione peroxidase (GPx) mimics. These series of compounds were well characterized by H-NMR, 1 13C-NMR and ESI-MS. Using different ROOH (H2O2, cumene hydroperoxide) for testing the antioxidizing properties of these com- pounds, we have found that from generation 0 to 2, the activity of the dendritic GPx mimics first de- creased and then increased. This can be explained on the basis of a greater steric hindrance, going from generation 0 to 1, and stronger binding interactions going from generation 1 to 2. In other words, there exists a balance between binding interactions and steric hindrance that may optimize the GPx activity.展开更多
The active center of human glutaredoxin(hGrx1)shares a common thioredoxin fold and specific affinity for substrate glutathione (GSH)with natural glutathione peroxidase(GPx).hGrx1 was redesigned to introduce the cataly...The active center of human glutaredoxin(hGrx1)shares a common thioredoxin fold and specific affinity for substrate glutathione (GSH)with natural glutathione peroxidase(GPx).hGrx1 was redesigned to introduce the catalytic selenocysteine residue to imi- tate the function of antioxidant selenoenzyme GPx in vivo.The human hGrx1 scaffold is a good candidate for potential medical application compared with other animal-originated protein scaffolds.Two consecutive rare codons(AGG-AGG)in the open reading frame of hGrx1 mRNA encoding Arg26-Arg27 residues can reduce seleno-hGrx1 expression level significantly in the Cys auxotrophic Escherichia coli strain BL21cysE51.Therefore,we optimized the rare codons,which resulted in a remarkable in- crease of the expression level in the Cys auxotrophic cells,which may be sufficient for future medical production.The engineered artificial selenoenzyme displays high GPx catalytic activity,rivaling that of some natural GPx proteins.Kinetic analysis of the engineered seleno-hGrx1 showed a typical ping-pong kinetic mechanism;its catalytic properties are similar to those of some nat- urally occurring GPx proteins.展开更多
The development of green and renewable energy sources is in high demand due to energy shortage and productivity development.Artificial photosynthesis(AP)is one of the most effective ways to address the energy shortage...The development of green and renewable energy sources is in high demand due to energy shortage and productivity development.Artificial photosynthesis(AP)is one of the most effective ways to address the energy shortage and the greenhouse effect by converting solar energy into hydrogen and other carbon-based high value-added products through the understanding of the mechanism,structural analysis,and functional simulation of natural photosynthesis.In this review,the development of AP from natural catalysts to artificial catalysts is described,and the processes of oxygen production,hydrogen production,and carbon fixation are sorted out to understand the properties and correlations of the core functional components in natural photosynthesis,to provide a better rational design and optimization for further development of advanced heterogeneous materials.展开更多
基金supported by the National Natural Science Foundation of China (Nos.22161142015,22105056).
文摘Natural protein channels have evolved with fantastic spatial structures,which play pivotal physiological functions in all living systems.Learning from nature,chemical scientists have developed a myriad of artificial transmembrane ion channels by using various chemical strategies,among which the non-covalent supramolecular ion channels exhibit remarkable advantages over other forms(e.g.,single-molecule ion channel),which exhibited facile preparation methods,easier structural modification and functionalization.In this review,we have systematically summarized the recent progress of supramolecular self-assembled artificial transmembrane ion channels,which were classified by different self-assembly mechanisms,such as hydrogen bonds,π-πinteractions,etc.Detailed preparation process and self-assembly strategies of the supramolecular ion channels have been described.Moreover,potential biomedical applications of the supramolecular ion channels have also been carefully discussed in this review.Finally,future opportunities and challenges facing this field were also elaborately discussed.It is anticipated that this review could provide a panoramic sketch and future directions towards the construction of novel artificial ion channels with novel functions and biomedical applications.
基金the National Natural Science Foundation of China (Grant Nos 20534030 and 20725415)National Basic Research Program of China (Grant No. 2007CB808006) Innovative Research Team in University of China (Grant No. IRT0422)
文摘Glutathione peroxidase (GPx, EC1.11.1.9), an important anti-oxidative selenoenzyme, can catalyze the reduction of harmful hydroperoxides with concomitant glutathione, thereby protecting cells and other biological issues against oxidative damage. It captures considerable interest in redesign of its function for either the mechanism study or the pharmacological development as an antioxidant. In order to de- velop a general strategy for specifically targeting and operating selenium in active sites of enzymes, the catalytically essential residue selenocysteine (Sec) was first successfully bioincorporated into the catalytic center of subtilisin by using an auxotrophic expression system. The studies of the catalytic activity and the steady-state kinetics demonstrated that selenosubtilisin is an excellent GPx-like bio- catalyst. In comparison with the chemically modified method, biosynthesis exhibits obvious advan- tages: Sec could be site-directly incorporated into active sites of enzymes to overcome the non-speci- ficity generated by chemical modification. This study provides an important strategy for specifically targeting and operating selenium in the active site of an enzyme.
基金financial support from the National Natural Science Foundation of China(91027023,21234004,21274051,21221063,21004028)the 111 project(B06009)
文摘Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved during the processes catalyzed by enzymes. It is plausible that the entire macromolecular scaffold is involved in catalysis via cooperative motions that result in incredible catalytic efficiency. Moreover, some enzymes can very strongly bind the transition state with an association constant of up to 1024 M-1, suggesting that covalent bond formation is a possible process during the conversion of the transition state in enzyme catalysis, in addition to the concatenation of noncovalent interactions. Supramolecular chemistry provides fundamental knowledge about the relationships between the dynamic structures and functions of organized molecules. By tak-ing advantage of supramolecular concepts, numerous supramolecular enzyme mimics with complex and hierarchical structures have been designed and investigated. Through the study of supramolecular enzyme models, a great deal of information to aid our understanding of the mechanism of catalysis by natural enzymes has been acquired. With the development of supramolec-ular artificial enzymes, it is possible to replicate the features of natural enzymes with regards to their constitutional complexity and cooperative motions, and eventually decipher the conformation-based catalytic mystery of natural enzymes.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.20334010,20474035,20473045,20574040 and 20573042)the Flemish government,the University of Leuyen and the F.W.0.Vlaanderen(Grant No.BIL 02/03).
文摘We have described the synthesis of a series of poly(aryl ether) dendrimers with telluride in the core and oligo(ethylene oxide) chains at the pe- riphery which act as glutathione peroxidase (GPx) mimics. These series of compounds were well characterized by H-NMR, 1 13C-NMR and ESI-MS. Using different ROOH (H2O2, cumene hydroperoxide) for testing the antioxidizing properties of these com- pounds, we have found that from generation 0 to 2, the activity of the dendritic GPx mimics first de- creased and then increased. This can be explained on the basis of a greater steric hindrance, going from generation 0 to 1, and stronger binding interactions going from generation 1 to 2. In other words, there exists a balance between binding interactions and steric hindrance that may optimize the GPx activity.
基金supported by the National Natural Science Foundation of China(91027023,20874036,20921003,and 21004028)the Natural Science Foundation for the Youth(21004028)+2 种基金the Natural Science Foundation of China for Outstanding Younger Scientist(20725415)the 111 pro-ject(B06009)the National Basic Research Program(2007CB808006)
文摘The active center of human glutaredoxin(hGrx1)shares a common thioredoxin fold and specific affinity for substrate glutathione (GSH)with natural glutathione peroxidase(GPx).hGrx1 was redesigned to introduce the catalytic selenocysteine residue to imi- tate the function of antioxidant selenoenzyme GPx in vivo.The human hGrx1 scaffold is a good candidate for potential medical application compared with other animal-originated protein scaffolds.Two consecutive rare codons(AGG-AGG)in the open reading frame of hGrx1 mRNA encoding Arg26-Arg27 residues can reduce seleno-hGrx1 expression level significantly in the Cys auxotrophic Escherichia coli strain BL21cysE51.Therefore,we optimized the rare codons,which resulted in a remarkable in- crease of the expression level in the Cys auxotrophic cells,which may be sufficient for future medical production.The engineered artificial selenoenzyme displays high GPx catalytic activity,rivaling that of some natural GPx proteins.Kinetic analysis of the engineered seleno-hGrx1 showed a typical ping-pong kinetic mechanism;its catalytic properties are similar to those of some nat- urally occurring GPx proteins.
基金This work was supported by the National Natural Science Foundation of China(Nos.2211101029,22001054,22075065)the National Key R&D Program of China(Nos.2020YFA0908500,2018YFA0901600)the Scientific Research Start-up Foundation of Hangzhou Normal University,China(Nos.2019QDL026,2019QDL025,2019QDL024).
文摘The development of green and renewable energy sources is in high demand due to energy shortage and productivity development.Artificial photosynthesis(AP)is one of the most effective ways to address the energy shortage and the greenhouse effect by converting solar energy into hydrogen and other carbon-based high value-added products through the understanding of the mechanism,structural analysis,and functional simulation of natural photosynthesis.In this review,the development of AP from natural catalysts to artificial catalysts is described,and the processes of oxygen production,hydrogen production,and carbon fixation are sorted out to understand the properties and correlations of the core functional components in natural photosynthesis,to provide a better rational design and optimization for further development of advanced heterogeneous materials.
