STRUCTURAL INSIGHTS AND ANTICANCER POTENTIAL OF MELITTIN IN CD147 INTERACTION

Year 2024, , 912 - 919, 10.09.2024

Barış Denk

https://doi.org/10.33483/jfpau.1405409

Abstract

Objective: This study investigates the interaction between melittin (PDB ID: 2MLT), a bioactive peptide from honeybee venom, and CD147 (PDB ID: 5XF0), a glycosylated transmembrane protein implicated in tumor progression.
Material and Method: Employing molecular docking and bioinformatics tools, our structural analysis reveals diverse binding features, including hydrogen bonds, salt bridges, and non-bonded contacts, between the CD147 complex and melittin.
Result and Discussion: Non-bonded interactions between 2MLT and specific amino acids (Gly181 and Arg201) of CD147 are highlighted, resembling aspects of the CypA/CD147 binding mechanism (Pro180-Gly181 and Arg201). The elevated anticancer potential of 2MLT was substantiated by utilizing the AntiCP 2.0 server and the ENNAACT server, employing machine learning and artificial neural network algorithms. Additionally, hydrophobicity analysis aligns with characteristics associated with anticancer peptides. Notably, thermodynamic stability variations with temperature underscore the robust binding affinity of 2MLT to the 5XF0 receptor. While our study comprehensively explores molecular interactions and predictive analyses, further in vitro and in vivo investigations are crucial to validate these findings for potential therapeutic applications.

Keywords

Anticancer peptides, CD147, cyclophilins, melittin, molecular docking

MELİTTİN’İN CD147 İLE ETKİLEŞİMİNE YAPISAL BAKIŞ VE ANTİKANSER POTANSİYELİ

Abstract

Amaç: Bu çalışma, arı zehrinden elde edilen biyoaktif bir peptit olan melittin (PDB ID: 2MLT) ile tümör ilerlemesinde rol oynayan bir glikozile transmembran protein olan CD147 (PDB ID: 5XF0) arasındaki etkileşimi incelemektedir.
Gereç ve Yöntem: Moleküler bağlanma ve biyoinformatik araçlar kullanılarak yürütülen yapısal analizimiz, CD147 kompleksi ile melittin arasında hidrojen bağları, tuz köprüleri ve bağlanmamış temaslar dahil olmak üzere çeşitli bağlanma özelliklerini ortaya çıkarmaktadır.
Sonuç ve Tartışma: 2MLT ile CD147'nin belirli amino asitleri (Gly181 ve Arg201) arasındaki etkileşimlerin, CypA/CD147 bağlanma mekanizmasına (Pro180-Gly181 ve Arg201) benzer şekilde oluştuğu gözlemlenmiştir. 2MLT'nin yüksek antikanser potansiyeli, AntiCP 2.0 server ve ENNAACT server kullanılarak, makine öğrenimi ve yapay sinir ağı algoritmalarını içeren yöntemlerle desteklenmiştir. Ayrıca, hidrofobiklik analizi, antikanser peptitlerle ilişkilendirilen özelliklerle uyumludur. Özellikle, sıcaklıkla olan termodinamik stabilite değişiklikleri, 2MLT'nin 5XF0 reseptörüne güçlü bağlanma eğilimini vurgulamaktadır. Çalışmamız, moleküler etkileşimlerin kapsamlı bir keşfini ve analizlerini sunarken, bu bulguların potansiyel terapötik uygulamalar için geçerliliğini doğrulamak için ileri in vitro ve in vivo çalışmalarının zorunlu olduğunu belirtmektedir.

Keywords

Antikanser peptidler, CD147, melittin, moleküler bağlanma, siklofilinler

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