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

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 TechniqueAbstractPolymorphism 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.

Penentuan Struktur Tiga Dimensi dan Profil Hasil Hidrolisis Protein Alergen Arginin Kinase Secara in silico

“…Berat molekul peptida yang telah mengalami hidrolisis menggunakan enzim kimotripsin ialah 3740 Da yang tidak bersifat alergen. Hal tersebut sesuai dengan penelitian Widodo et al (2018), menjelaskan bahwa kimotripsin aktif dengan memotong peptida ujung N yang mengandung fenilalanin (F), tirosin (Y) dan triptopan (W). Jumlah fragmen yang dihasilkan dari pemotongan menggunakan enzim tripsin adalah 43 fragmen peptida.…”

Extraction of Collagen from the Skin of Kacang Goat and Production of Its Hydrolysate as an Inhibitor of Angiotensin Converting Enzyme

“…The enzymes used for hydrolysis include pepsin, trypsin, and chymotrypsin (Sujarwanto et al, 2018;Winarti et al, 2019). The hydrolysis using various digestive enzymes have shown to be able to produce bioactive peptide compounds as antihypertensive agents from the animal products such as meat of buffalo (Sujarwanto et al, 2018), foot of chicken (Bravo et al, 2019), milk of goat (Widodo et al, 2019), the meat of rabbit (Permadi et al, 2019), and meat of duck (Winarti et al, 2019). The bioactive peptide is able to inhibit the activity of angiotensin converting enzyme in the RAAS system (Renin-Angiotensin-Aldosterone System), which causes hypertension due to the constriction of blood vessels (Hsueh and Wyne, 2011).…”

Identification of Goats’ and Cows’ Milk Protein Profile in Banyumas Regency by Sodium Dedocyl Sulphate Gel Electrophoresis (Sds-Page)

“…Beta casein is classified as casein that is sensitive to calcium ions in milk, so it is related to the yield quantity of cheese produced (Damian et al, 2008). In addition, beta casein is known to associate with therapeutic properties that produce bioactive peptides (Widodo et al, 2018). There are parts of the beta casein sequence that can produce bioactive peptioda if digested by humans.…”

“…For instance, a higher quantity of casein kappa has positively reduced the time for cheese coagulation, allowing a faster production process (Prizenberg et al, 2005). Instead of conventional drugs, functional food can even be produced from milk protein fraction to lower high blood pressure (Widodo et al, 2018). These are the challenges in dairy industry in Indonesia.…”