CASPASE: REVIEW TENTANG PERAN LAIN PADA APOPTOSIS, KARAKTER KANTUNG KATALITIK, SERTA INTERAKSI DENGAN SUBSTRAT DAN INHIBITORNYA

Maryam Hasymia Ishmatullah, Sandra Megantara, Jutti Levita

Abstract


Akhir-akhir ini banyak dilakukan penelitian tentang penghambatan pertumbuhan sel kanker atau apoptosis dari ekstrak tanaman. Caspase, enzim protease yang berperan dalam apoptosis, menjadi target menarik untuk ditelaah. Penelusuran artikel ini dilakukan untuk memberi informasi tentang peran lain caspase pada apoptosis, karakter kantung katalitiknya, serta interaksinya dengan substrat dan inhibitor. Metode pencarian artikel dilakukan melalui basis data Google Scholar dengan kata kunci “caspase catalytic siteâ€, “apoptosisâ€, “amino acid residuesâ€, dan “substrates and inhibitors of caspaseâ€. Hasil penelusuran artikel ini menunjukkan bahwa caspase-3 berperan dalam sensitivitas dan efisiensi apoptosis serta menghambat produksi ROS, sedangkan caspase 9 dapat membelah protein pro-apoptosis menjadi bentuk aktifnya. Kantung katalitik masing-masing caspase memiliki residu penting berbeda, yaitu residu Cys285 dan His23 pada caspase-3, Asp374 pada caspase-8, dan pada caspase 9 berupa residu Cys230, His224, Cys272, His237, Cys239, dan Cys287.  Substrat caspase-3 adalah DEVD dan DVLD dan inhibitornya yaitu FICA dan DICA bersifat alosterik. Substrat caspase-8 adalah IETD dan saat ini sedang dikembangkan inhibitornya yakni c-FLIP. LEHD adalah substrat caspase-9, serta seng merupakan inhibitor selektif caspase-9.  Dapat disimpulkan bahwa selain berperan dalam apoptosis, caspase juga meningkatkan sensitivitas dan efisiensi apoptosis serta menghambat produksi ROS. Walaupun secara umum karakter kantung katalitik caspase mirip, namun masing-masing caspase memiliki residu asam amino penting yang berbeda, dan masing-masing caspase memiliki inhibitor yang menempati posisi alosterik (bukan menghambat di tempat substrat terikat). Review ini akan bermanfaat bagi peneliti bidang penemuan obat antikanker.

Kata kunci: antikanker, apoptosis, caspase


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DOI: http://dx.doi.org/10.52434/jfb.v12i2.1154

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