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Identifikasi Mekanisme Fungsional Senyawa Bioaktif Peptida dari Organisme Laut sebagai Inhibitor Alami Angiotensin-I Converting Enzyme (ACE) secara In silico

DOI: https://doi.org/10.20956/mff.v24i1.9647
Article History

Submited : March 15, 2020
Published : July 1, 2020

Inhibitor alami Angiotensin-I Converting Enzyme (ACE) berbasis peptida bioaktif saat ini menjadi fokus penelitian karena sifatnya yang unik dan memilki berbagai peran biologis penting diantaranya adalah sebagai kandidat pengobatan hipertensi. Terdapat beberapa peptida bioaktif yang dihasilkan oleh organisme laut dan telah terbukti mampu menghambat enzim ACE, antara lain peptida bioaktif yang berasal dari udang (SV, IF, dan WP) serta peptida bioaktif yang berasal dari ikan hiu (CF, EY, MF, dan FE). Pada penelitian ini dilakukan identifikasi, evaluasi, dan eksplorasi terhadap interaksi yang terjadi antara molekul peptida bioaktif dengan makromolekul ACE secara in silico menggunakan motode penambatan molekuler berbasis protein-peptida. Sekuensing peptida bioaktif dimodelkan menjadi konformasi 3D terlebih dahulu menggunakan software PEP-FOLD. Konformasi terbaik dipilih untuk kemudian dilakukan studi interaksi molekuler terhadap makromolekul ACE menggunakan software PatchDock. Interaksi molekuler yang terjadi diamati lebih lanjut menggunakan software BIOVIA Discovery Studio 2020.  Berdasarkan hasil dari penambatan molekuler berbasis protein-peptida, peptida bioaktif CF dan IF yang berasal dari udang dan peptida bioaktif MF yang berasal dari ikan hiu memiliki afinitas yang baik, yaitu dengan ACE score masing-masing adalah −380,62 kJ/mol, −436,43 kJ/mol, dan −349,91 kJ/mol. Dengan demikian, peptida bioaktif laut tersebut diprediksi dapat dipilih sebagai kandidat inhibitor alami enzim ACE berbasis peptida sebagai alternatif antihipertensi.

References

  1. Aleman A, Gimenez B, Perez-Santin E, Gomez-Guillen MC, Montero P. Contribution of Leu and Hyp residues to antioxidant and ACE-inhibitory activities of peptide sequences isolated from squid gelatin hydrolysate. Food Chem. 2011;125(2):334-341. DOI:10.1016/j.foodchem.2010.08.058
  2. Tikellis C, Bernardi S, Burns WC. Angiotensinconverting enzyme 2 is a key modulator of the reninangiotensin system in cardiovascular and renal disease. Curr Opin Nephrol Hypertens. 2011;20(1): 62-68. DOI:10.1097/MNH.0b013e328341164a
  3. Silberbauer K, Stanek B, Templ H. Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition. Br J Clin Pharmacol. 1982;14:S87–S93. DOI:10.1111/j.1365-2125.1982.tb02063.x
  4. Wood R. Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study. Br J Clin Pharmacol. 1995;39(3):265-270. DOI:10.1111/j.1365-2125.1995.tb04447.x
  5. Li GH, Le GW, Shi YH, Shrestha S. Angiotensin I-converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects. Nutr Res. 2004;24(7):469-486. DOI:10.1016/j.nutres.2003.10.014
  6. Wang W, Shen S, Chen Q, Tanga B, He G, Ruan H, Das UN. Hydrolyzates of Silkworm pupae (bombyx mori) protein is a new source of angiotensin I-converting enzyme inhibitory peptides (ACEIP). Curr Pharm Biotechnol. 2008;9(4):307-314. DOI:10.2174/138920108785161578
  7. Wu Q, Jia J, Yan H, Du J, Gui Z. A novel angiotensin-I converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study. Peptides. 2015;68:17-24. DOI:10.1016/j.peptides.2014.07.026
  8. Li P, Jia J, Fang M, Zhang L, Guo M, Xie J, Xia Y, Zhou L, Wei D. In vitro and in vivo ACE inhibitory of pistachio hydrolysates and in silico mechanism of identified peptide binding with ACE. Process Biochem. 2014;49(5):898-904. DOI: 10.1016/j.procbio.2014.02.007
  9. Asoodeh A, Haghighi L, Chamani J, Ansari-Ogholbeyk MA, Mojallal-Tabatabaei Z, Lagzian M. Potential angiotensin I-converting enzyme inhibitory peptides from gluten hydrolysate: biochemical characterization and molecular docking study. J Cereal Sci. 2014;60(1):92-98. DOI: 10.1016/j.jcs.2014.01.019
  10. Jia J, Wu Q, Yan H, Gui Z. Purification and molecular docking study of a novel angiotensin-I converting enzyme (ACE) inhibitory peptide from alcalase hydrolysate of ultrasonic-pretreated silkworm pupa (Bombyx mori) protein. Process Biochem. 2015;50(5):876-883. DOI: 10.1016/j.procbio.2014.12.030
  11. Izawa H, Aoyagi Y. Inhibition of angiotensin converting enzyme by mushroom. J JPN Soc Food Sci. 2006;53(9):459-465. DOI:10.3136/nskkk.53.459
  12. Kiyoto M, Saito S, Hattori K, Cho N, Hara T, Yagi Y, Aoyama M. Inhibitory effects of lpipecolic acid from the edible mushroom, Sarcodon aspratus, on angiotensin I-converting enzyme. J Wood Sci. 2008;54(2):179-181. DOI:10.1007/s10086-007-0923-7
  13. Jang JH, Jeong SC, Kim JH, Lee YH, Ju YC, Lee JS. Characterisation of a new antihypertensive angiotensin I-converting enzyme inhibitory peptide from Pleurotus cornucopiae. Food Chem. 2011;127(2):412-418. DOI:10.1016/j.foodchem.2011.01.010
  14. Wu H, He HL, Chen XL, Sun CY, Zhang YZ, Zhou BC. Purification and identification of novel angiotensinI-converting enzyme inhibitory peptides from shark meat hydrolysate. Process Biochem. 2008;43(4):457-461. DOI:10.1016/j.procbio.2008.01.018
  15. Kleekayai T, Harnedy PA, O’Keeffe MB, Poyarkov AA, CunhaNeves A, Suntornsuk W, FitzGerald RJ. Extraction of antioxidant and ACE inhibitory peptides from Thai traditional fermented shrimp pastes. Food Chem. 2015;176:441-447. DOI:10.1016/j.foodchem.2014.12.026
  16. Wu H, He HL, Chen XL, Sun CY, Zhang YZ, Zhou BC. Purification and identification of novel angiotensinI-converting enzyme inhibitory peptides from shark meat hydrolysate. Process Biochem. 2008; 43(4): 457-461. DOI:10.1016/j.procbio.2008.01.018
  17. Fortin J, Karam A. Effect of a commercial peat mossshrimp wastes compost on pucinellia growth in red mud. Int J Min Reclam Env. 1998;12(3):105-109. DOI:10.1080/09208118908944032
  18. Fagbenro OA, Bello-Olusoji OA. Preparation, nutrient composition and digestibility of fermented shrimp head silage. Food Chem. 1997;60(4):489-493. DOI:10.1016/S0308-8146(96)00314-7
  19. Coward-Kelly G, Agbogbo FK, Holtzapple MT. Lime treatment of shrimp head waste for the generation of highly digestible animal feed. Bioresour Technol. 2006;97(13):1515-1520. DOI:10.1016/j.biortech.2005.06.014
  20. Manni L, Ghorbel-Bellaaj O, Jellouli K, Younes I, Nasri M. Extraction and characterization of chitin, chitosan, and protein hydrolysates prepared from shrimp waste by treatment with crude protease from Bacillus cereus SV1. Appl Biochem Biotechnol. 2010;162(2):345-357. DOI:10.1007/s12010-009-8846-y
  21. Sanchez-Camargo AP, Martinez-Correa HA, Paviani LC, Cabral FA. Supercritical CO2 extraction of lipids and astaxanthin from Brazilian redspotted shrimp waste (Farfantepenaeus paulensis). J Supercrit Fluid. 2011;56(2): 164-173. DOI:10.1016/j.supflu.2010.12.009
  22. Sachindra NM, Bhaskar N, Mahendrakar NS. Recovery of carotenoids from shrimp waste in organic solvents. J Waste Manag. 2006;26(10):1092-1098. DOI:10.1016/j.wasman.2005.07.002
  23. Akif M, Masuyer G, Schwager SLU, Bhuyan BJ, Mugesh G, Isaac RE, Sturrock ED, Acharya KR. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril. FEBS J. 2011;278(19):3644-3650. DOI:10.1111/j.1742-4658.2011.08276.x
  24. Wang X, Yu H, Xing R, Li P. Characterization, preparation, and purification of marine bioactive peptides. Biomed Res Int. 2017;2017:9746720. DOI:10.1155/2017/9746720
  25. Kurniawan F, Miura Y, Kartasasmita RE, Yoshioka N, Mutalib A, Tjahjono DH. In silico study, synthesis, and cytotoxic activities of porphyrin derivatives. Pharmaceuticals. 2018;11(1):8. DOI:10.3390/ph11010008
  26. 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. DOI:10.1371/journal.pone.0121860
  27. Kemmish H, Fasnacht M, Yan L. Fully automated antibody structure prediction using BIOVIA tools: Validation study. PLoS One. 2017;12(5): e0177923. DOI:10.1371/journal.pone.0177923
  28. 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). DOI:10.3390/ijms19020386
  29. Prabhu DS, 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.
  30. Thevenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tuffery P. PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 2012;40:288–293. DOI:10.1093/nar/gks419
  31. Shen Y, Maupetit J, Derreumaux P, Tuffery P. Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput. 2014;10(10):4745–4758. DOI:10.1021/ct500592m
  32. Veeraragavan V, Narayanaswamy R, 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):383–386. DOI:10.22159/ajpcr.2017.v10i11.20999
  33. 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. 2001;10(11):2147–2161. DOI:10.22159/10.1110/ps.12901
Fakih, T. M., & Dewi, M. L. (2020). Identifikasi Mekanisme Fungsional Senyawa Bioaktif Peptida dari Organisme Laut sebagai Inhibitor Alami Angiotensin-I Converting Enzyme (ACE) secara In silico. Majalah Farmasi Dan Farmakologi, 24(1), 17-21. https://doi.org/10.20956/mff.v24i1.9647

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