دورية أكاديمية
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Temperature effect in the inhibition of PLA 2 activity of Bothrops brazili venom by Rosmarinic and Chlorogenic acids, experimental and computational approaches.

التفاصيل البيبلوغرافية
العنوان: Temperature effect in the inhibition of PLA 2 activity of Bothrops brazili venom by Rosmarinic and Chlorogenic acids, experimental and computational approaches.
المؤلفون: Diniz EADS; Institute of Chemistry, Federal University of Rio Grande do Norte, Av Senador Salgado Filho, Natal-RN, Brazil., da Silva DP; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, Petrópolis, Natal, Brazil., Ferreira SS; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, Petrópolis, Natal, Brazil., Fernandes-Pedrosa MF; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, Petrópolis, Natal, Brazil., Vieira DS; Institute of Chemistry, Federal University of Rio Grande do Norte, Av Senador Salgado Filho, Natal-RN, Brazil.
المصدر: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Jul; Vol. 42 (10), pp. 5238-5252. Date of Electronic Publication: 2023 Jun 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE
أسماء مطبوعة: Publication: June 2012- : Oxon, UK : Taylor & Francis
Original Publication: Guilderland, NY : Adenine Press, [c1983-
مواضيع طبية MeSH: Depsides*/chemistry , Depsides*/pharmacology , Rosmarinic Acid* , Bothrops* , Cinnamates*/chemistry , Cinnamates*/pharmacology , Molecular Docking Simulation* , Phospholipases A2*/chemistry , Phospholipases A2*/metabolism , Molecular Dynamics Simulation* , Temperature* , Chlorogenic Acid*/chemistry , Chlorogenic Acid*/pharmacology, Animals ; Phospholipase A2 Inhibitors/chemistry ; Phospholipase A2 Inhibitors/pharmacology ; Crotalid Venoms/chemistry ; Crotalid Venoms/antagonists & inhibitors ; Crotalid Venoms/enzymology ; Protein Binding ; Hydrogen Bonding
مستخلص: Myotoxicity caused by snakebite envenoming emerges as one of the main problems of ophidic accidents as it is not well neutralized by the current serum therapy. A promising alternative is to search for efficient small molecule inhibitors that can act against multiple venom components. Phospholipase A 2 (PLA 2 ) is frequently found in snake venom and is usually associated with myotoxicity. Thus it represents an excellent target for the search of new treatments. This work reports the effect of temperature in the inhibition of catalytic properties of PLA 2 from Bothrops brazili venom by Rosmarinic (RSM) and Chlorogenic (CHL) acids through experimental and computational approaches. Three temperatures were evaluated (25, 37 and 50 °C). In the experimental section, enzymatic assays showed that RSM is a better inhibitor in all three temperatures. At 50 °C, the inhibition efficiency decayed significantly for both acids. Docking studies revealed that both ligands bind to the hydrophobic channel of the protein dimer where the phospholipid binds in the catalytic process, interacting with several functional residues. In this context, RSM presents better interaction energies due to stronger interactions with chain B of the dimer. Molecular dynamics simulations showed that RSM can establish selective interactions with ARG112B of PLA 2 , which is located next to residues of the putative Membrane Disruption Site in PLA2-like structures. The affinity of RSM and CHL acids towards PLA 2 is mainly driven by electrostatic interactions, especially salt bridge interactions established with residues ARG33B (for CHL) and ARG112B (RSM) and hydrogen bonds with residue ASP89A. The inability of CHL to establish a stable interaction with ARG112B was identified as the reason for its lower inhibition efficiency compared to RSM at the three temperatures. Furthermore, extensive structural analysis was performed to explain the lower inhibition efficiency at 50 °C for both ligands. The analysis performed in this work provides important information for the future design of new inhibitors.Communicated by Ramaswamy H. Sarma.
فهرسة مساهمة: Keywords: Molecular dynamics; chlorogenic acid; enzymatic inhibition; phospholipase A2; rosmarinic acid
تواريخ الأحداث: Date Created: 20230628 Date Completed: 20240519 Latest Revision: 20240519
رمز التحديث: 20240520
DOI: 10.1080/07391102.2023.2226912
PMID: 37378497
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-0254
DOI:10.1080/07391102.2023.2226912