Jin Young Lee, Hoe-Suk Lee, Yu-Young Lee, Mi-Hyang Kim, Hyun-Joo Kim, Narae Han, Moon Seok Kang, Young Joo Yeon
{"title":"通过动力学和结构分析全面研究黄酮类化合物对α-葡萄糖苷酶的抑制机制","authors":"Jin Young Lee, Hoe-Suk Lee, Yu-Young Lee, Mi-Hyang Kim, Hyun-Joo Kim, Narae Han, Moon Seok Kang, Young Joo Yeon","doi":"10.1007/s12257-024-00018-4","DOIUrl":null,"url":null,"abstract":"<p>Flavonoid consists of an extensive range of compounds with variable inhibitory activities against alpha-glucosidase, implicating its role in the prevention and treatment of diabetes caused by uncontrolled increases in the blood glucose level. Comprehensive study on a selected assortment of flavonoids for their degrees of inhibition, types of inhibitory mode and the structure–function relationship both in terms of the ligand chemical structure and in the context of the enzyme–inhibitor binding complex is therefore necessary to predict and develop efficient flavonoid inhibitors. Herein, flavonoids based on flavone, flavonol, flavanone and isoflavone skeletons in their aglycone and glycone forms were analyzed to this purpose. Most aglycones showed excellent inhibition, while glycones showed relatively low activities. Competitive, noncompetitive and mixed inhibition modes were observed from different types of flavonoids, and their molecular mechanisms by binding to the active or allosteric sites of alpha-glucosidase were analyzed via the docking study. Quercetin with a superior competitive inhibitory activity bound near the catalytic residues within the active site, whereas other glycosylated quercetin derivatives bound at more distal sites. Mixed inhibitors resulted in opposite binding conformations in the allosteric site depending on whether they show more competitive-like or uncompetitive-like behaviors, while the noncompetitive inhibitor could bind in both conformations.</p>","PeriodicalId":8936,"journal":{"name":"Biotechnology and Bioprocess Engineering","volume":"203 1","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comprehensive study on the inhibition mechanism of alpha-glucosidase by flavonoids via kinetic and structural analysis\",\"authors\":\"Jin Young Lee, Hoe-Suk Lee, Yu-Young Lee, Mi-Hyang Kim, Hyun-Joo Kim, Narae Han, Moon Seok Kang, Young Joo Yeon\",\"doi\":\"10.1007/s12257-024-00018-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Flavonoid consists of an extensive range of compounds with variable inhibitory activities against alpha-glucosidase, implicating its role in the prevention and treatment of diabetes caused by uncontrolled increases in the blood glucose level. Comprehensive study on a selected assortment of flavonoids for their degrees of inhibition, types of inhibitory mode and the structure–function relationship both in terms of the ligand chemical structure and in the context of the enzyme–inhibitor binding complex is therefore necessary to predict and develop efficient flavonoid inhibitors. Herein, flavonoids based on flavone, flavonol, flavanone and isoflavone skeletons in their aglycone and glycone forms were analyzed to this purpose. Most aglycones showed excellent inhibition, while glycones showed relatively low activities. Competitive, noncompetitive and mixed inhibition modes were observed from different types of flavonoids, and their molecular mechanisms by binding to the active or allosteric sites of alpha-glucosidase were analyzed via the docking study. Quercetin with a superior competitive inhibitory activity bound near the catalytic residues within the active site, whereas other glycosylated quercetin derivatives bound at more distal sites. Mixed inhibitors resulted in opposite binding conformations in the allosteric site depending on whether they show more competitive-like or uncompetitive-like behaviors, while the noncompetitive inhibitor could bind in both conformations.</p>\",\"PeriodicalId\":8936,\"journal\":{\"name\":\"Biotechnology and Bioprocess Engineering\",\"volume\":\"203 1\",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biotechnology and Bioprocess Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1007/s12257-024-00018-4\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology and Bioprocess Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s12257-024-00018-4","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Comprehensive study on the inhibition mechanism of alpha-glucosidase by flavonoids via kinetic and structural analysis
Flavonoid consists of an extensive range of compounds with variable inhibitory activities against alpha-glucosidase, implicating its role in the prevention and treatment of diabetes caused by uncontrolled increases in the blood glucose level. Comprehensive study on a selected assortment of flavonoids for their degrees of inhibition, types of inhibitory mode and the structure–function relationship both in terms of the ligand chemical structure and in the context of the enzyme–inhibitor binding complex is therefore necessary to predict and develop efficient flavonoid inhibitors. Herein, flavonoids based on flavone, flavonol, flavanone and isoflavone skeletons in their aglycone and glycone forms were analyzed to this purpose. Most aglycones showed excellent inhibition, while glycones showed relatively low activities. Competitive, noncompetitive and mixed inhibition modes were observed from different types of flavonoids, and their molecular mechanisms by binding to the active or allosteric sites of alpha-glucosidase were analyzed via the docking study. Quercetin with a superior competitive inhibitory activity bound near the catalytic residues within the active site, whereas other glycosylated quercetin derivatives bound at more distal sites. Mixed inhibitors resulted in opposite binding conformations in the allosteric site depending on whether they show more competitive-like or uncompetitive-like behaviors, while the noncompetitive inhibitor could bind in both conformations.
期刊介绍:
Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.