High-Risk Polymorphisms Associated with the Molecular Function of Human HMGCR Gene Infer the Inhibition of Cholesterol Biosynthesis.
HMG-CoA reductase or HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) is a rate-limiting enzyme involved in cholesterol biosynthesis. HMGCR plays an important role in the possible occurrence of hypercholesterolemia leading to atherosclerosis and coronary heart disease. This enzyme is a major target...
| Publicado en: | BioMed Research International pp. 1 - 18 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
6/6/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=157287402&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 157287402 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 6/6/2022 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 157287402 157287402 157287402 10.1155/2022/4558867 157287402 ppf: 1 ppct: 17 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: High-Risk Polymorphisms Associated with the Molecular Function of Human HMGCR Gene Infer the Inhibition of Cholesterol Biosynthesis. aug: au: Das, Keshob Chandra Hossain, Mohammad Uzzal Moniruzzaman, Md Salimullah, Md Akhteruzzaman, Sharif affil: Molecular Biotechnology Division, National Institute of Biotechnology, Ganakbari, Ashulia, Savar, Dhaka-1349, Bangladesh sug: subj: Cholesterol Metabolism Polymorphism, Genetic Polymorphism, Single Nucleotide Genes Risk Assessment Human Female Male Molecular Biology Molecular Docking Simulation Sequence Analysis Mutation Outcome Assessment Descriptive Statistics Female Male ab: HMG-CoA reductase or HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) is a rate-limiting enzyme involved in cholesterol biosynthesis. HMGCR plays an important role in the possible occurrence of hypercholesterolemia leading to atherosclerosis and coronary heart disease. This enzyme is a major target for cholesterol-lowering drugs such as "statin" which blocks the synthesis of mevalonate, a precursor for cholesterol biosynthesis. This study is aimed at characterizing deleterious mutations and classifying functional single nucleotide polymorphisms (SNPs) of the HMGCR gene through analysis of functional and structural evaluation, domain association, solvent accessibility, and energy minimization studies. The functional and characterization tools such as SIFT, PolyPhen, SNPs and GO, Panther, I-Mutant, and Pfam along with programming were employed to explore all the available SNPs in the HMGCR gene in the database. Among 6815 SNP entries from different databases, approximately 388 SNPs were found to be missense. Analysis showed that seven missense SNPs are more likely to have deleterious effects. A tertiary model of the mutant protein was constructed to determine the functional and structural effects of the HMGCR mutation. In addition, the location of the mutations suggests that they may have deleterious effects because most of the mutations are residing in the functional domain of the protein. The findings from the analysis predicted that rs147043821 and rs193026499 missense SNPs could cause significant structural and functional instability in the mutated proteins of the HMGCR gene. The findings of the current study will likely be useful in future efforts to uncover the mechanism and cause of hypercholesterolemia. In addition, the identified SNPs of HMGCR gene could set up a strong foundation for further therapeutic discovery. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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