Dillip K Senapati, D Jagadeesh Kumar, Priya Narayan, Nagendra H G, Venkatesha M A, Govindaraju M, K R K Easwaran, K V Ramanathan, S Raghothama
{"title":"AICD 中心 12 个残基肽段的结构分析及其与金属和多酚的相互作用,作为治疗注意力缺失症的潜在药物靶点。","authors":"Dillip K Senapati, D Jagadeesh Kumar, Priya Narayan, Nagendra H G, Venkatesha M A, Govindaraju M, K R K Easwaran, K V Ramanathan, S Raghothama","doi":"10.1080/07391102.2023.2245044","DOIUrl":null,"url":null,"abstract":"<p><p>Structural analysis of the central 12 residue stretch of Amyloid precursor protein Intracellular Domain (AICD<sub>16-27</sub>: T-S-I-H-H-G-V-V-E-V-D-A) was carried out by NMR and homology modeling. Further, metal and polyphenol interactions were also carried out for these 12 residues stretch, as it contains two critical Histidine residues, which were observed to be perturbed <i>via</i> NMR. A full length 57 residues AICD model was generated <i>via</i> computational methods, to ascertain its overall conformation, as the entire structure was unavailable. An overlay of this AICD entire model with the full length Aβ-42 structure matched well, implying similar properties. Docking studies with metals and polyphenols indicated involvement of the key Histidine residues highlighting their roles towards neurodegeneration and AD pathophysiology.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structural analysis of the AICD central 12 residue peptide stretch and its interactions with metals and polyphenols, as a potential drug target for AD.\",\"authors\":\"Dillip K Senapati, D Jagadeesh Kumar, Priya Narayan, Nagendra H G, Venkatesha M A, Govindaraju M, K R K Easwaran, K V Ramanathan, S Raghothama\",\"doi\":\"10.1080/07391102.2023.2245044\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Structural analysis of the central 12 residue stretch of Amyloid precursor protein Intracellular Domain (AICD<sub>16-27</sub>: T-S-I-H-H-G-V-V-E-V-D-A) was carried out by NMR and homology modeling. Further, metal and polyphenol interactions were also carried out for these 12 residues stretch, as it contains two critical Histidine residues, which were observed to be perturbed <i>via</i> NMR. A full length 57 residues AICD model was generated <i>via</i> computational methods, to ascertain its overall conformation, as the entire structure was unavailable. An overlay of this AICD entire model with the full length Aβ-42 structure matched well, implying similar properties. Docking studies with metals and polyphenols indicated involvement of the key Histidine residues highlighting their roles towards neurodegeneration and AD pathophysiology.Communicated by Ramaswamy H. Sarma.</p>\",\"PeriodicalId\":15272,\"journal\":{\"name\":\"Journal of Biomolecular Structure & Dynamics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomolecular Structure & Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/07391102.2023.2245044\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomolecular Structure & Dynamics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/07391102.2023.2245044","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Structural analysis of the AICD central 12 residue peptide stretch and its interactions with metals and polyphenols, as a potential drug target for AD.
Structural analysis of the central 12 residue stretch of Amyloid precursor protein Intracellular Domain (AICD16-27: T-S-I-H-H-G-V-V-E-V-D-A) was carried out by NMR and homology modeling. Further, metal and polyphenol interactions were also carried out for these 12 residues stretch, as it contains two critical Histidine residues, which were observed to be perturbed via NMR. A full length 57 residues AICD model was generated via computational methods, to ascertain its overall conformation, as the entire structure was unavailable. An overlay of this AICD entire model with the full length Aβ-42 structure matched well, implying similar properties. Docking studies with metals and polyphenols indicated involvement of the key Histidine residues highlighting their roles towards neurodegeneration and AD pathophysiology.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.