Identifikasi Mekanisme Fungsional Senyawa Bioaktif Peptida dari Organisme Laut sebagai Inhibitor Alami Angiotensin-I Converting Enzyme (ACE) secara In silico
Abstract
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
Downloads
Published
Issue
Section
License
The copyright to this article is transferred to Universitas Hasanuddin (UNHAS) if and when the article is accepted for publication. The undersigned hereby transfers all rights in and to the paper including without limitation all copyrights to UNHAS. The undersigned hereby represents and warrants that the paper is original and that he/she is the author of the paper, except for material that is clearly identified as to its original source, with permission notices from the copyright owners where required. The undersigned represents that he/she has the power and authority to make and execute this assignment.
We declare that:
- This paper has not been published in the same form elsewhere.
- It will not be submitted anywhere else for publication prior to acceptance/rejection by this Journal.
- A copyright permission is obtained for materials published elsewhere and which require this permission for reproduction.
Furthermore, I/We hereby transfer the unlimited rights of publication of the above-mentioned paper in whole to UNHAS The copyright transfer covers the exclusive right to reproduce and distribute the article, including reprints, translations, photographic reproductions, microform, electronic form (offline, online) or any other reproductions of similar nature.
The corresponding author signs for and accepts responsibility for releasing this material on behalf of any and all co-authors. This agreement is to be signed by at least one of the authors who have obtained the assent of the co-author(s) where applicable. After submission of this agreement signed by the corresponding author, changes of authorship or in the order of the authors listed will not be accepted.
