Jurnal pangan nasional "terakreditasi" Kemeristekdikti dari Indonesian Food Technologists® - IFT

DOI: https://doi.org/10.17728/jatp.3008

Mengidentifikasi Peptida Bioaktif Angiotensin Converting Enzyme-inhibitor (ACEi) dari Kasein β Susu Kambing dengan Polimorfismenya Melalui Teknik In Silico

*Hermawan Setyo Widodo orcid  -  Fakultas Peternakan, Universitas Jenderal Soedirman, Purwokerto, Indonesia
Tridjoko Wisnu Murti  -  Fakultas Peternakan, Universitas Gadjah Mada, Yogyakarta, Indonesia
Ali Agus  -  Fakultas Peternakan, Universitas Gadjah Mada, Yogyakarta, Indonesia
Widodo Widodo  -  Fakultas Peternakan, Universitas Gadjah Mada, Yogyakarta, Indonesia

Citation Format:
Abstract

Susu kambing memiliki komponen protein salah satunya protein β dan secara umum terjadi polimorfisme pada level protein. Perubahan urutan asam amino akibat polimorfisme memungkinkan adanya potensi dihasilkannya peptida bioaktif penghambat enzim pengubah angiotensin (ACEi). Penelitian ini bertujuan untuk menyaring peptida bioaktif yang berpotensi sebagai ACEi dari kasein β kambing beserta polimorfismenya. Penelitian ini dilakukan dengan teknik in silico terhadap sekuen kasein β kambing serta struktur tiga dimensi human testicular ACE. Langkah yang dilakukan dalam penelitian ini meliputi simulasi pemotongan peptida dengan enzim pencernaan (pepsin, tripsin dan kimotripsin), peninjauan karakteristik peptida lalu simulasi docking ligan-reseptor. Tampilan parameter Lipinski’s Rule of Five (Ro5), bioaktivitas dan energi afinitas dipertimbangkan untuk memilih peptida bioaktif. Hasil yang didapat menunjukkan bahwa ditemukan peptida bioaktif yakni INK (Ile-Asp-Lys) yang memiliki kemampuan hampir setara dengan lisinopril (afinitas energi -8,2kkal/mol vs. -8,3kkal/mol). Peptida INK dapat ditemukan dari hasil hidrolisis dari alel A, C, D dan E, sehingga polimorfisme tidak menyebabkan perbedaan produksi peptida bioaktif. Kesimpulan yang dapat diambil yakni kasein β susu kambing jika dicerna dengan enzim pencernaan dapat menghasilkan peptida bioaktif ACEi yakni INK.

Identification of Angiotensin Converting Enzyme-inhibitor (ACEi) Bioactive Peptide from Goat Milk β-Casein with It's Polymorphism by In Silico Technique

Abstract

Polymorphism eventually may be occurred at the protein level. Changes in the amino acid sequence due to polymorphism may exhibit a potential action to generate of the angiotensin-converting enzyme inhibitors (ACEi) bioactive peptide. This study is aimed to assess bioactive peptides that have a great potent value as ACEi from goat β casein along with its polymorphism. The research was done by in silico technique on goat β-casein sequence and three-dimensional structure human testicular ACE. Peptide-cutting simulations with digestive enzymes (pepsin, trypsin and chymotrypsin), peptide properties review, then ligand-receptor docking simulations was applied in this research. Appearance of Lipinski's Rule of Five (Ro5), bioactivity and affinity energy were considered for selecting bioactive peptides. The results show that bioactive peptide found as INK (Ile-Asp-Lys) which had similar ability as lisinopril (energy affinity –8.2kcal/mol vs. –8.3kcal/mol). The INK peptides could be found from the hydrolysis resulted in alleles A, C, D and E, therefore polymorphism did not affect the differences of production of bioactive peptides. A conclusion, processed goat milk β casein with digestive enzymes could produce ACEi of INK as bioactive peptide.

Fulltext View|Download
Keywords: susu kambing; ACEi; kasein β; peptida bioaktif; in silico; goat milk; ACEi; β casein; bioactive peptides

Article Metrics:

Article Info
Section: Artikel Penelitian (Research Article)
Language : ID-ID
Recent articles
Peranan Daun Kumis Kucing (Orthosiphon stamineus Benth) dalam Mengeliminasi Kandungan Cd dan Pb pada Dada Ayam Broiler Pengaruh Penambahan Beberapa Konsentrasi Gula terhadap Stabilitas Warna Ekstrak Antosianin Buah Rukem (Flacourtia rukam Zoll. & Mor.) Aktivitas Antioksidan, BAL, Viskositas dan Nilai L*a*b* dalam Yogurt Drink Sinbiotik antara Bifidobacterium Longum dengan Buah Naga Merah (Hylocereus polyrhizus) Aktivitas Penangkalan Radikal Bebas dan Kemampuan Reduksi Ekstrak Kulit Kayu Akway (Drimys piperita Hook. f.) More recent articles
  1. Benet, L.Z., Hosey, C.M., Ursu, O., Oprea, T.I. 2016. BDDCS, the rule of 5 and drugability. Advanced Drug Delivery Reviews 101(1): 89-98. DOI: 10.1016/j.addr.2016.05.007
  2. Caroli, A., Chiatti, F., Chessa, S., Rignanese, D., Bolla, P., Pagnacco, G. 2006. Focusing on the goat casein complex. Journal of Dairy Science 89:3178-3187. DOI: 10.3168/jds.S0022-0302(06)72592-9
  3. Gao, H.N., Zhao, S.G., Zheng, N., Zhang, Y.D., Wang, S.S., Zhou, X.Q., Wang, J.Q. 2017. Combination of histidine, lysine, methionine, and leucine promotes β-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells. Journal of Dairy Science 100(9): 7696-7709. DOI: 10.3168/jds.2015-10729
  4. Haque, E., Chand, R. 2008. Antihypertensive and antimicrobial bioactive peptides from milk proteins. European Food Research Technology 227(1): 7–15. DOI: 10.1007/s00217-007-0689-6
  5. Hermanto, S. 2016. Virtual screening peptida bioaktif antihipertensi dari hidrolisat kasein susu kambing etawa. Alchemy: Journal of Chemistry 5(2): 45-54. DOI: 10.18860/al.v5i2.3671
  6. Husain, A., Ahmad, A., Khan, S.A., Asif, M., Bhutani, R., Al-Abbasi, F.A. 2016. Synthesis, molecular properties, toxicity, and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents. Saudi Pharmaceutical Journal 24(1): 104-114. DOI: 10.1016/j.jsps.2015.02.008
  7. Iwaniak, A., Minkiewicz, P., Darewicz, M.. 2014. Food‐originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction. Comprehensive Reviews in Food Science and Food Safety 13(2): 144-134. DOI: 10.1111/1541-4337.12051
  8. Jedhe, G.S., Sanjayan, G.J. 2017. Chapter 6 - Structural Design for Bioactive Peptides in Peptide-based Drug Discovery : Challenges and New Therapeutics. Srivastava, V. (ed.). Royal Society of Chemistry, London. DOI: 10.1039/9781788011532-00172
  9. Johnston, N., Dettmar, P.W., Bishwokarma, B., Lively, M.O., Koufman, J.A. 2007. Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. The Laryngoscope. 117 (6): 1036–9. DOI: 10.1097/MLG.0b013e31804154c3
  10. Kaminski, S., Cieslinska, A., Kostyra, E. 2007. Polymorphism of bovine beta-casein and its potential effect on human health. Journal of Applied Genetics 48(3): 189-198. DOI: 10.1007/BF03195213
  11. Kim, R., Skolnick, J. 2008. Assesment of programs for ligand binding affinity prediction. Journal of Computational Chemistry 29(8): 1316-1331. DOI: 10.1002/jcc.20893
  12. Lee, K.J., Kim, S.B., Ryu, J.S., Shin, H.S., Lim, J.W. 2005. Separation and purification of angiotensin converting enzyme inhibitory peptides derived from goat’s milk casein hydrolysates. Asian-Australasian Journal of Animal Science 18(5): 741-746. DOI: 10.5713/ajas.2005.741
  13. Marletta, D., Criscione, A., Bordonaro, S., Guastella, A.M., D’Urso, G. 2007. Casein polymorphism in goat’s milk (Review). Lait 87: 491-504. DOI: 10.1051/lait:2007034
  14. Morris, G.M., Huey, R., Olson, A.J. 2008. Using AutoDock for ligand-receptor docking. Current Protocols in Bioinformatics 24 (8): 8.14.1-8.14.40. DOI: 10.1002/0471250953.bi0814s24
  15. Muhammad, S.A., Fatima, N. 2015. In silico analysis and molecular docking studies of potential angiotensin‑converting enzyme inhibitor using quercetin glycosides. Pharmacognosy Magazine 11(42): 123-126. DOI: 10.4103/0973-1296.157712
  16. Năsalean, A., Ognean, L., Muntean, S., Bâlici, Ş., Matei, H. 2017. Comparative analysis of electrophoretic profile of major proteins of milk from Alpine and Carpathian goats. Bulletin UASVM Veterinary Medicine 74(1): 20-25. DOI: 10.15835/buasvmcn-vm:12447
  17. Park., Y.W., Juárez, M., Ramos, M., Haenlein, G.F.W. 2007. Physico-chemical characteristics of goat and sheep milk. Small Rumuminant Research 68(1-2): 88-113. DOI: 10.1016/j.smallrumres.2006.09.013
  18. Petrat-Melin, B., Andersen, P., Rasmussen, J.T., Poulsen, N.A., Larsen, L.B. Young, J.F. 2015. In vitro digestion of purified β -casein variants A1, A2, B, and I: effects on antioxidant and angiotensin-converting enzyme inhibitory capacity. Journal of Dairy Science 98: 15-26. DOI: 10.3168/jds.2014-8330
  19. Rahajeng, E., Tuminah, S. 2009. Pervalensi hipertensi dan determinannya di Indonesia. Majalah Kedokteran Indonesia 59(12): 580-587
  20. Rodriguez, J., Gupta, N., Smith, R.D., Peyzner, P.A. 2008. Does trypsin cut before proline?. Journal of Proteome Research. 7 (1): 300-305. DOI: 10.1021/pr0705035
  21. Salem, S.A., El-Agamy, E.I., Salama, F.A., Abo-Soliman, N.H. 2009. Short note : Isolation, molecular and biochemical characterization of goat milk casein and its fraction. Tropical and Subtropical Agrosystems 11(1): 29-35
  22. Wang, Z., Zhang, S., Wang, W., Feng, F., Shan, W. 2011. A novel Angiotensin I Converting Enzyme inhibitory peptide from the milk casein: virtual screening and docking studies. Agricultural Sciences in China 10(3): 463-467. DOI: 10.1016/S1671-2927(11)60026-6
  23. Weimann, C., Meisel, H., Erhardt, G. 2009. Short communication: bovine κ-casein result in different angiotensin I converting enzyme (ACE) inhibitory peptides. Journal of Dairy Science 92:1885-1888. DOI: 10.3168/jds.2008-1671
  24. Wijesekara, I., S. Kim. 2010. Angiotensin-I-Converting Enzyme (ACE) inhibitors from marine resources: prospects in the pharmaceutical industry. Marine Drugs 8(4): 1080-1093. DOI: 10.3390/md8041080

Last update:

No citation recorded.

Last update:

No citation recorded.