In silico analyses of deleterious missense SNPs of human apolipoprotein E3

Abstract ApoE3 is the major chylomicron apolipoprotein, binding in a specific liver peripheral cell receptor, allowing transport and normal catabolism of triglyceride-rich lipoprotein constituents. Point mutations in ApoE3 have been associated with Alzheimer’s disease, type III hyperlipoproteinemia,...

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Autores principales:	Allan S. Pires, William F. Porto, Octavio L. Franco, Sérgio A. Alencar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43e3c748c0db48c28f20a0cab69056a9
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spelling	oai:doaj.org-article:43e3c748c0db48c28f20a0cab69056a92021-12-02T16:07:00ZIn silico analyses of deleterious missense SNPs of human apolipoprotein E310.1038/s41598-017-01737-w2045-2322https://doaj.org/article/43e3c748c0db48c28f20a0cab69056a92017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01737-whttps://doaj.org/toc/2045-2322Abstract ApoE3 is the major chylomicron apolipoprotein, binding in a specific liver peripheral cell receptor, allowing transport and normal catabolism of triglyceride-rich lipoprotein constituents. Point mutations in ApoE3 have been associated with Alzheimer’s disease, type III hyperlipoproteinemia, atherosclerosis, telomere shortening and impaired cognitive function. Here, we evaluate the impact of missense SNPs in APOE retrieved from dbSNP through 16 computational prediction tools, and further evaluate the structural impact of convergent deleterious changes using 100 ns molecular dynamics simulations. We have found structural changes in four analyzed variants (Pro102Arg, Arg132Ser, Arg176Cys and Trp294Cys), two of them (Pro102Arg and Arg176Cys) being previously associated with human diseases. In all cases, except for Trp294Cys, there was a loss in the number of hydrogen bonds between CT and NT domains that could result in their detachment. In conclusion, data presented here could increase the knowledge of ApoE3 activity and be a starting point for the study of the impact of variations on APOE gene.Allan S. PiresWilliam F. PortoOctavio L. FrancoSérgio A. AlencarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Allan S. Pires William F. Porto Octavio L. Franco Sérgio A. Alencar In silico analyses of deleterious missense SNPs of human apolipoprotein E3
description	Abstract ApoE3 is the major chylomicron apolipoprotein, binding in a specific liver peripheral cell receptor, allowing transport and normal catabolism of triglyceride-rich lipoprotein constituents. Point mutations in ApoE3 have been associated with Alzheimer’s disease, type III hyperlipoproteinemia, atherosclerosis, telomere shortening and impaired cognitive function. Here, we evaluate the impact of missense SNPs in APOE retrieved from dbSNP through 16 computational prediction tools, and further evaluate the structural impact of convergent deleterious changes using 100 ns molecular dynamics simulations. We have found structural changes in four analyzed variants (Pro102Arg, Arg132Ser, Arg176Cys and Trp294Cys), two of them (Pro102Arg and Arg176Cys) being previously associated with human diseases. In all cases, except for Trp294Cys, there was a loss in the number of hydrogen bonds between CT and NT domains that could result in their detachment. In conclusion, data presented here could increase the knowledge of ApoE3 activity and be a starting point for the study of the impact of variations on APOE gene.
format	article
author	Allan S. Pires William F. Porto Octavio L. Franco Sérgio A. Alencar
author_facet	Allan S. Pires William F. Porto Octavio L. Franco Sérgio A. Alencar
author_sort	Allan S. Pires
title	In silico analyses of deleterious missense SNPs of human apolipoprotein E3
title_short	In silico analyses of deleterious missense SNPs of human apolipoprotein E3
title_full	In silico analyses of deleterious missense SNPs of human apolipoprotein E3
title_fullStr	In silico analyses of deleterious missense SNPs of human apolipoprotein E3
title_full_unstemmed	In silico analyses of deleterious missense SNPs of human apolipoprotein E3
title_sort	in silico analyses of deleterious missense snps of human apolipoprotein e3
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/43e3c748c0db48c28f20a0cab69056a9
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_version_	1718384771241869312

In silico analyses of deleterious missense SNPs of human apolipoprotein E3

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