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

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology and Bioprocess Engineering Pub Date : 2024-02-15 DOI:10.1007/s12257-024-00018-4
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}
引用次数: 0

摘要

黄酮类化合物种类繁多,对α-葡萄糖苷酶具有不同的抑制活性,在预防和治疗因血糖水平失控升高而引起的糖尿病方面发挥着重要作用。因此,为了预测和开发高效的类黄酮抑制剂,有必要从配体化学结构和酶-抑制剂结合复合物的角度,对精选的各类类黄酮化合物的抑制程度、抑制模式类型和结构-功能关系进行全面研究。为此,我们分析了基于黄酮、黄酮醇、黄烷酮和异黄酮骨架的苷元和糖元形式的类黄酮。大多数苷元显示出极好的抑制作用,而糖醛酸则显示出相对较低的活性。研究人员观察了不同类型黄酮的竞争性、非竞争性和混合抑制模式,并通过对接研究分析了它们与α-葡萄糖苷酶的活性位点或异生位点结合的分子机制。竞争性抑制活性较强的槲皮素与活性位点内的催化残基附近结合,而其他糖基化的槲皮素衍生物则与较远的位点结合。混合抑制剂在异构位点的结合构象截然相反,这取决于它们表现出的是竞争性抑制剂还是非竞争性抑制剂,而非竞争性抑制剂则可以两种构象结合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biotechnology and Bioprocess Engineering
Biotechnology and Bioprocess Engineering 工程技术-生物工程与应用微生物
CiteScore
5.00
自引率
12.50%
发文量
79
审稿时长
3 months
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.
期刊最新文献
Assessing the applicability of tunicate skin-extracted cellulose as a base material for ultrasound gel Fabrication of protein–inorganic biohybrid as an imageable drug delivery system comprising transferrin, green fluorescent protein, and copper phosphate Continuous cell recycling in methylotrophic yeast Pichia pastoris to enhance product yields: a case study with Yarrowia lipolytica lipase Lip2 Sensitive detection of SARS-CoV2 spike antibodies by a paper-based polypyrrole/reduced graphene oxide sensor A neural ordinary differential equation model for predicting the growth of Chinese Hamster Ovary cell in a bioreactor system
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1