Two naturally occurring mutations at the first and second bases of codon aspartic acid 156 in the proposed catalytic triad of human lipoprotein lipase. In vivo evidence that aspartic acid 156 is essential for catalysis.

H, Y; Bruin, T.; Tuzgöl, S.; Wilson, Bonnie I.; Roederer, Ghislaine O.; Liu, M S; Davignon, Jean; Kastelein, John J.P.; Brunzell, John D.; Hayden, Michael R.

doi:10.1016/s0021-9258(18)46034-6

Cited by 42 publications

(1 citation statement)

References 31 publications

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“…Table shows the predicted binding free energies and interactions of residues among LPL, orlistat, and polyphenols. The catalytic domain of lipase superfamily enzymes, such as LPL, adopts an α/β-hydrolase fold, and the active site catalytic triad (Ser-His-Asp/Glu) is well conserved. − The pocket of 6OB0, which contains the catalytic triad (Ser159, Asp183, and His268), was considered to be the active site, and a docking calculation centered on Ser159 was performed. The calculation showed that all polyphenols used in this study could bind to the active site, similar to the orlistat lipase inhibitor (Figure ).…”

Section: Resultsmentioning

confidence: 99%

New Insights into Polyphenols in Plants as Potential Modulators of Atherosclerosis by Acting on Lipoprotein Lipase: In Silico Molecular Docking and In Vitro Studies

Oogai

Hamashima

Yamasaki

et al. 2022

ACS Food Sci. Technol.

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Epidemiological studies have shown that polyphenols that are widely distributed in vegetables and fruits reduce the risk of cardiovascular diseases, which are caused by altered lipoprotein metabolism. Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Although the antioxidant and anti-inflammatory activities of polyphenols are known, little is known about the effects of polyphenols on lipoprotein metabolism via LPL activity. Therefore, the aim of this study was to determine the effects of polyphenols on LPL activity using in silico molecular docking and in vitro studies. The polyphenols investigated here included quercetin, rutin, and apigenin. When measured by in silico molecular docking, some polyphenols, such as quercetin, rutin, and naringin, provided a low docking energy, suggesting that they may inhibit the LPL activity by interacting with Ser159 and His268, the catalytic residues of LPL. An in vitro study subsequently showed that the investigated polyphenols tended to have lower LPL activities, and their inhibitory activities were greater than that of orlistat, a commercially available inhibitor of LPL. Additionally, the degree of inhibition in vitro was positively and significantly related to the binding energy of polyphenols in silico. The structure–inhibitory activity relationship also suggested the possibility that the structure of the B ring, rather than the A and C rings, may be more important in regulating LPL activity. In conclusion, in addition to its antioxidant and anti-inflammatory activities, because LPL is involved in the uptake of lipids into arteries from the systemic circulation, we propose that polyphenols may in part diminish the risk of cardiovascular disease by inhibiting LPL activity in arteries.

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Section: Resultsmentioning

confidence: 99%

New Insights into Polyphenols in Plants as Potential Modulators of Atherosclerosis by Acting on Lipoprotein Lipase: In Silico Molecular Docking and In Vitro Studies

Oogai

Hamashima

Yamasaki

et al. 2022

ACS Food Sci. Technol.

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Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries

Liu

Chitayat

et al. 1994

Hum. Mutat.

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Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg243His mutation while the patients of German and French descent have a novel Arg243Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg243Cys substitution which together with the Arg243His mutation would implicate three recurrent mutations involving the first and second nucleotides of the codon encoding Arg243 of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene.

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Genetic Mutations Affecting Human Lipoproteins, Their Receptors, and Their Enzymes

Zannis

Kardassis

Zanni

1993

Advances in Human Genetics 21

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Two naturally occurring mutations at the first and second bases of codon aspartic acid 156 in the proposed catalytic triad of human lipoprotein lipase. In vivo evidence that aspartic acid 156 is essential for catalysis.

Cited by 42 publications

References 31 publications

New Insights into Polyphenols in Plants as Potential Modulators of Atherosclerosis by Acting on Lipoprotein Lipase: In Silico Molecular Docking and In Vitro Studies

New Insights into Polyphenols in Plants as Potential Modulators of Atherosclerosis by Acting on Lipoprotein Lipase: In Silico Molecular Docking and In Vitro Studies

Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries

Genetic Mutations Affecting Human Lipoproteins, Their Receptors, and Their Enzymes

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