Identifikasi Mekanisme Molekuler Senyawa Bioaktif Peptida Laut sebagai Kandidat Inhibitor Angiotensin-I Converting Enzyme (ACE)

Taufik Muhammad Fakih, Mentari Luthfika Dewi

Abstrak


Senyawa bioaktif peptida laut saat ini menjadi fokus penelitian karena memiliki sifat yang unik. Salah satu peran biologis penting dari senyawa peptida tersebut adalah sebagai agen antihipertensi terhadap aktivitas Angiotensin-I Converting Enzyme (ACE). Terdapat beberapa senyawa peptida yang telah terbukti mampu menghambat reseptor ACE, seperti senyawa peptida yang dihasilkan oleh teripang (Acaudina molpadioides), kerang biru (Mytilus edulis), dan ikan tuna (Thunnini). Dalam penelitian ini dilakukan identifikasi dan evaluasi terhadap interaksi yang terjadi antara senyawa peptida dengan reseptor ACE menggunakan motode penambatan molekuler berbasis protein-peptida. Sequencing senyawa peptida dimodelkan terlebih dahulu menggunakan server PEP-FOLD. Konformasi terbaik dipilih untuk dilakukan studi interaksi terhadap makromolekul reseptor ACE menggunakan software PatchDock. Interaksi yang terjadi diamati lebih lanjut menggunakan software BIOVIA Discovery Studio 2020. Berdasarkan hasil dari penambatan molekuler berbasis protein-peptida, senyawa peptida kerang biru dan ikan tuna memiliki afinitas yang baik terhadap reseptor ACE, yaitu dengan ACE score masing-masing adalah −391,62 kJ/mol dan −516,56 kJ/mol. Dengan demikian, senyawa bioaktif peptida laut tersebut diprediksi dapat dipilih sebagai kandidat inhibitor reseptor ACE berbasis peptida

Kata Kunci


antihipertensi; senyawa bioaktif peptida laut; inhibitor Angiotensin-I Converting Enzyme (ACE); pola penghambatan; penambatan molekuler berbasis protein-peptida.

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Referensi


Destoumieux-Garzón D, Rosa RD, Schmitt P, Barreto C, Vidal-Dupiol J, Mitta G, et al. Antimicrobial peptides in marine invertebrate health and disease. Philos Trans R Soc B Biol Sci. 2016;371(1695):20150300. https://doi.org/10.1098/rstb.2015.0300

Hamed I, Özogul F, Özogul Y, Regenstein JM. Marine Bioactive Compounds and Their Health Benefits: A Review. Compr Rev Food Sci Food Saf. 2015;14(4):446-65. https://doi.org/10.1111/1541-4337.12136

Lordan S, Ross RP, Stanton C. Marine bioactives as functional food ingredients: Potential to reduce the incidence of chronic diseases. Marine Drugs. 2011;9(6):1056-100. https://doi.org/10.3390/md9061056

Yu F, Zhang Z, Luo L, Zhu J, Huang F, Yang Z, et al. Identification and molecular docking study of a novel angiotensin-I converting enzyme inhibitory peptide derived from enzymatic hydrolysates of cyclina sinensis. Mar Drugs. 2018;16(11):411. https://doi.org/10.3390/md16110411

Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60. https://doi.org/10.1016/S0140-6736(12)61766-8

Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Arkani M. RAS Genetic Variants in Interaction with ACE Inhibitors Drugs Influences Essential Hypertension Control. Arch Med Res. 2017;48(1):88-95. https://doi.org/10.1016/j.arcmed.2017.03.003

Regoli D, Gobeil F. Critical insights into the beneficial and protective actions of the kallikrein-kinin system. Vascular Pharmacology. 2015;64:1-10. https://doi.org/10.1016/j.vph.2014.12.003

Zhang P, Roytrakul S, Sutheerawattananonda M. Production and purification of glucosamine and angiotensin-I converting enzyme (ACE) inhibitory peptides from mushroom hydrolysates. J Funct Foods. 2017;36:72-83. https://doi.org/10.1016/j.jff.2017.06.049

Igic R, Behnia R. Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease. Curr Pharm Des. 2007;13(12):1199-214. https://doi.org/10.2174/138161207780618876

Elavarasan K, Shamasundar BA, Badii F, Howell N. Angiotensin I-converting enzyme (ACE) inhibitory activity and structural properties of oven- and freeze-dried protein hydrolysate from fresh water fish (Cirrhinus mrigala). Food Chem. 2016;206:210-16. https://doi.org/10.1016/j.foodchem.2016.03.047

Acharya KR, Sturrock ED, Riordan JF, Ehlers MRW. ACE revisited: A new target for structure-based drug design. Nature Reviews Drug Discovery. 2003;2(11):891-902. https://doi.org/10.1038/nrd1227

Zhao Y, Li B, Dong S, Liu Z, Zhao X, Wang J, et al. A novel ACE inhibitory peptide isolated from Acaudina molpadioidea hydrolysate. Peptides. 2009;30(6):1028-33. https://doi.org/10.1016/j.peptides.2009.03.002

Je JY, Park PJ, Byun HG, Jung WK, Kim SK. Angiotensin I converting enzyme (ACE) inhibitory peptide derived from the sauce of fermented blue mussel, Mytilus edulis. Bioresour Technol. 2005;96(14):1624-9. https://doi.org/10.1016/j.biortech.2005.01.001

Lee SH, Qian ZJ, Kim SK. A novel angiotensin I converting enzyme inhibitory peptide from tuna frame protein hydrolysate and its antihypertensive effect in spontaneously hypertensive rats. Food Chem. 2010;118(1):96-102. https://doi.org/10.1016/j.foodchem.2009.04.086

Wang X, Yu H, Xing R, Li P. Characterization, Preparation, and Purification of Marine Bioactive Peptides. BioMed Research International. 2017;2017:9746720. https://doi.org/10.1155/2017/9746720

Natesh R, Schwager SLU, Sturrock ED, Acharya KR. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature. 2003;421(6922):551-4. https://doi.org/10.1038/nature01370

Chavan SG, Deobagkar DD. An in silico insight into novel therapeutic interaction of LTNF peptide-LT10 and design of structure based peptidomimetics for putative anti-diabetic activity. PLoS One. 2015;10(3):e0121860. https://doi.org/10.1371/journal.pone.0121860

Kurniawan F, Miura Y, Kartasasmita RE, Mutalib A, Yoshioka N, Tjahjono DH. In silico study, synthesis, and cytotoxic activities of porphyrin derivatives. Pharmaceuticals. 2018;11(1):8. https://doi.org/10.3390/ph11010008

Kemmish H, Fasnacht M, Yan L. Fully automated antibody structure prediction using BIOVIA tools: Validation study. PLoS One. 2017;12(5): e0177923. https://doi.org/10.1371/journal.pone.0177923

Aruleba RT, Adekiya TA, Oyinloye BE, Kappo AP. Structural Studies of Predicted Ligand Binding Sites and Molecular Docking Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer. Int J Mol Sci. 2018;19(2). https://doi.org/10.3390/ijms19020386

Sathya D, Rajeswari VD. In Silico docking analysis of bioactive compounds from Chinese medicine Jinqi Jiangtang Tablet(JQJTT) using Patch Dock. J Chem Pharm Res. 2016;8(5):15-21.

Thévenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tufféry P. PEP-FOLD: An updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 2012;40(1):288-93. https://doi.org/10.1093/nar/gks419

Shen Y, Maupetit J, Derreumaux P, Tufféry P. Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput. 2014;10(10):4745-58. https://doi.org/10.1021/ct500592m

Guo F, Li SC, Wang L, Zhu D. Protein-protein binding site identification by enumerating the configurations. BMC Bioinformatics. 2012;13:158. https://doi.org/10.1186/1471-2105-13-158

Zhang C, Vasmatzis G, Cornette JL, DeLisi C. Determination of atomic desolvation energies from the structures of crystallized proteins. J Mol Biol. 1997;267(3):707-26. https://doi.org/10.1006/jmbi.1996.0859

Veeraragavan V, Radhakrishnan N, Chidambaram R. Predicting the biodegradability nature of imidazole and its derivatives by modulating two histidine degradation enzymes (urocanase and formiminoglutamase) activities. Asian J Pharm Clin Res. 2017;10(11):383-6. https://doi.org/10.22159/ajpcr.2017.v10i11.20999

Norel R, Sheinerman F, Petrey D, Honig B. Electrostatic contributions to protein-protein interactions: Fast energetic filters for docking and their physical basis. Protein Sci. 2008;10(11):2147-61. https://doi.org/10.1110/ps.12901




DOI: https://doi.org/10.25077/jsfk.7.1.76-82.2020

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