Tracing the GSAP-APP C-99 interaction site in the β-amyloid pathway leading to Alzheimer's disease

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dc.contributor.author Angira, Deekshi
dc.contributor.author Chikhale, Rupesh
dc.contributor.author Mehta, Kapilkumar
dc.contributor.author Bryce, Richard A.
dc.contributor.author Thiruvenkatam, Vijay
dc.date.accessioned 2019-07-16T10:04:24Z
dc.date.available 2019-07-16T10:04:24Z
dc.date.issued 2019-07
dc.identifier.citation Angira, Deekshi; Chikhale, Rupesh; Mehta, Kapilkumar; Bryce, Richard A. and Thiruvenkatam, Vijay, “Tracing the GSAP-APP C-99 interaction site in the β-amyloid pathway leading to Alzheimer's disease”, ACS Chemical Neuroscience, DOI: 10.1021/acschemneuro.9b00332, Jul. 2019. en_US
dc.identifier.issn 1948-7193
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/4624
dc.identifier.uri https://dx.doi.org/10.1021/acschemneuro.9b00332
dc.description.abstract Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer’s disease. It forms a ternary complex with γ secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 µM. Further, computational modeling of the GSAP - 719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex; APP C-99-GSAP- γ secretase. It paves a futuristic path to investigate the GSAP- APP C-99 binding in detail and accentuate the role of GSAP in the β-amyloid pathway. en_US
dc.description.statementofresponsibility by Deekshi Angira, Rupesh Chikhale, Kapilkumar Mehta, Richard A. Bryce and Vijay Thiruvenkatam
dc.language.iso en_US en_US
dc.publisher American Chemical Society en_US
dc.subject Alzheimer’s disease en_US
dc.subject β-amyloid pathway en_US
dc.subject ELISA en_US
dc.subject Dot blot far western en_US
dc.subject Isothermal titration calorimetry en_US
dc.subject Molecular dynamic simulation en_US
dc.title Tracing the GSAP-APP C-99 interaction site in the β-amyloid pathway leading to Alzheimer's disease en_US
dc.type Article en_US
dc.relation.journal dc.relation.journal


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