Probing Conformational Changes and Interfacial Recognition Site of Lipases With Surfactants and Inhibitors

Mateos-Diaz, Eduardo; Amara, Sawsan; Roussel, Alain; Longhi, Sonia; Cambillau, Christian; Carrière, Frédéric

doi:10.1016/bs.mie.2016.09.040

Cited by 22 publications

(19 citation statements)

References 69 publications

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“…Disulfide bridges formed between cysteine residues significantly contribute to conformational stability by decreasing the entropy of protein . Recently, a study has been reported on the conformational changes occurring in digestive lipases, fungal lipases, and cutinases in the presence of surfactants or inhibitors through X‐ray crystallographic studies …”

Section: Lipase Structure and Classificationmentioning

confidence: 99%

“…21 Recently, a study has been reported on the conformational changes occurring in digestive lipases, fungal lipases, and cutinases in the presence of surfactants or inhibitors through X-ray crystallographic studies. 47 Lipase-catalyzed reactions take place at the interface between the insoluble substrate and the aqueous phase, whereas the movement of lid allows the access of substrate to catalytic site. 52 The internal side of the lid facing the active site is hydrophobic whereas the external side is hydrophilic.…”

Section: Lipase Structurementioning

confidence: 99%

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Recent advances on sources and industrial applications of lipases

Sarmah

Revathi

Sheelu

et al. 2017

Biotechnology Progress

296

148

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Lipases are the industrially important biocatalysts, which are envisioned to have tremendous applications in the manufacture of a wide range of products. Their unique properties such as better stability, selectivity and substrate specificity position them as the most expansively used industrial enzymes. The research on production and applications of lipases is ever growing and there exists a need to have a latest review on the research findings of lipases. The present review aims at giving the latest and broadest overall picture of research and development on lipases by including the current studies and progressions not only in the diverse industrial application fields of lipases, but also with regard to its structure, classification and sources. Also, a special emphasis has been made on the aspects such as process optimization, modeling, and design that are very critical for further scale-up and industrial implementation. The detailed tabulations provided in each section, which are prepared by the exhaustive review of current literature covering the various aspects of lipase including its production and applications along with example case studies, will serve as the comprehensive source of current advancements in lipase research. This review will be very useful for the researchers from both industry as well as academia in promoting lipolysis as the most promising approaches to intensified, greener and sustainable processes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:5-28, 2018.

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Section: Lipase Structure and Classificationmentioning

confidence: 99%

Section: Lipase Structurementioning

confidence: 99%

Recent advances on sources and industrial applications of lipases

Sarmah

Revathi

Sheelu

et al. 2017

Biotechnology Progress

296

148

View full text Add to dashboard Cite

show abstract

“…The modeled structures of OVCA2 and its S. cerevisiae homologue FSH1 did not however contain a lid domain present in classic lipases. [17,[45][46][47] Instead, the structure of FSH1 had a small cap domain that did not undergo large scale rearrangement upon substrate binding. [23] Overall, the comprehensive enzymatic characterization of OVCA2 shows that it is an active metabolic serine hydrolase with high selectivity against short ester substrates, but high activity toward extended alkyl chain esters.…”

Section: Comprehensive Substrate Specificity Of Ovca2mentioning

confidence: 99%

Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae

et al. 2020

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Over 100 metabolic serine hydrolases are present in humans with confirmed functions in metabolism, immune response, and neurotransmission. Among potentially clinically-relevant but uncharacterized human serine hydrolases is OVCA2, a serine hydrolase that has been linked with a variety of cancer-related processes. Herein, we developed a heterologous expression system for OVCA2 and determined the comprehensive substrate specificity of OVCA2 against two ester substrate libraries. Based on this analysis, OVCA2 was confirmed as a serine hydrolase with a strong preference for long-chain alkyl ester substrates (>10-carbons) and high selectivity against a variety of short, branched, and substituted esters. Substitutional analysis was used to identify the catalytic residues of OVCA2 with a Ser117-His206-Asp179 classic catalytic triad. Comparison of the substrate specificity of OVCA2 to the model homologue FSH1 from Saccharomyces cerevisiae illustrated the tighter substrate selectivity of OVCA2, but their overlapping substrate preference for extended straight-chain alkyl esters. Conformation of the overlapping biochemical properties of OVCA2 and FSH1 was used to model structural information about OVCA2. Together our analysis provides detailed substrate specificity information about a previously, uncharacterized human serine hydrolase and begins to define the biological properties of OVCA2. OPEN ACCESS Citation: Bun JS, Slack MD, Schemenauer DE, Johnson RJ (2020) Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae. PLoS ONE 15(3): e0230166. https://doi.org/ 10.

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“…PL is a rather complex enzyme whose activity is controlled by quite a number of factors such as the substrate, the product, pH of medium, metal ions and accessibility to the usually lipophilic substrate (1,(9)(10)(11). Surfactants, represented in the body by biliary secretion, usually play a significant role in the action of PL in that they improve the interfacing between aqueous medium and essentially lipophilic substrates (11)(12)(13)(14). Moreover, PL was shown to have a special protein moiety that functions like a lid for the binding site, which can be open upon a trigger by the presence of an oily substrate (10,11,14).…”

mentioning

confidence: 99%

“…Surfactants, represented in the body by biliary secretion, usually play a significant role in the action of PL in that they improve the interfacing between aqueous medium and essentially lipophilic substrates (11)(12)(13)(14). Moreover, PL was shown to have a special protein moiety that functions like a lid for the binding site, which can be open upon a trigger by the presence of an oily substrate (10,11,14). Co-lipase is another protein subunit necessary for optimal action of PL in the presence of bile acids, which may otherwise inhibit the lipolytic action of the enzyme (10).…”

mentioning

confidence: 99%

Pancreatic lipase inhibitory activity of selected pharmaceutical agents

et al. 2018

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Twenty-five structurally diverse compounds have been tested in vitro for their pancreatic lipase (PL) inhibitory activity. Despite the diversity of tested compounds, the relationship comprising structural attributes of the compounds could be established to correlate with the observed inhibitory activity. Compounds that exerted inhibitory action through surface activity were of different profile from the rest of compounds. When co-incubated with orlistat (OsT), important synergistic effects for some compounds (orphenadrine, gliclazide, cefuroxime and sulfacetamide) were revealed, while antagonistic effects were demonstrated for others (camphor sulfonic acid and dinitro salicylic acid). Docking studies for the most active molecules were performed and molecular interaction forces with the PL active site were identified. The results suggested co-binding of OsT along with the other inhibitor in the binding site in cases of synergistic effect but not in the case of antagonistic effect. These results were additionally supported by affinity capillary electrophoresis. In conclusion, synergistic lipase inhibitory activity between OsT and some other pharmaceutical compounds was demonstrated for the first time, which might help improve the pharmacological effect of OsT.

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Probing Conformational Changes and Interfacial Recognition Site of Lipases With Surfactants and Inhibitors

Cited by 22 publications

References 69 publications

Recent advances on sources and industrial applications of lipases

Recent advances on sources and industrial applications of lipases

Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae

Pancreatic lipase inhibitory activity of selected pharmaceutical agents

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