Unveiling Anticancer Potential in the Interactions of Melittin Peptides with CD147 Receptor: A Structural and Functional Analysis of Ligand-Target Interactions

Barış Denk

doi:10.18016/ksutarimdoga.vi.1470524

EN TR

Unveiling Anticancer Potential in the Interactions of Melittin Peptides with CD147 Receptor: A Structural and Functional Analysis of Ligand-Target Interactions

Abstract

In this study, the anticancer potential of melittin (MLT) peptides interacting with the CD147 receptor was investigated through in silico structural and functional analyses. The interaction between the transmembrane glycoprotein CD147 and cyclophilin A (CypA) activates signaling pathways crucial in cancer pathology. This study focused on the potential of melittin peptides to inhibit this interaction. Structures of the CD147 receptor and melittin peptides were obtained from the Protein Data Bank (PDB), including the three-dimensional structure of the Ig1 domain of CD147 (PDB ID: 5XF0) and melittin structures (PDB IDs: 2MLT, 6O4M, 3QRX, 8AHT, and 8AHS). Validated ligand structures were acquired through X-ray crystallography. Receptor-ligand interactions and anticancer activity were evaluated using the ClusPro2.0 molecular docking server, AnciCP2.0 and ENNAACT anticancer analysis servers, ProtScale hydrophobicity analysis, PDBSum amino acid interaction analysis, and PRODIGY thermodynamic stability analysis tools. Molecular docking simulations analyzed receptor-ligand interactions, emphasizing the role of hydrophobic interactions. Structural analysis revealed variability in peptide quality, with 2MLT demonstrating favorable attributes while 3QRX exhibited weak integrity. Anticancer analysis servers indicated that 2MLT and 3QRX, exhibiting similar binding patterns with 5XF0 and CD147/CypA, may demonstrate potential anticancer activity. Specifically, non-bonded interactions involving Gly181 and Arg201 in the 5XF0-2MLT complex and non-bonded interactions involving Pro180, Gly181, and Arg201 in the 5XF0-3QRX complex were highlighted, resembling the interaction pattern of CD147/CypA. Therefore, the importance of understanding molecular interactions and guiding drug discovery through structural examinations and computational analyses was emphasized, providing insights into the anticancer effects and drug design implications of these complexes; moreover, further research into their structural determinants and therapeutic potentials is critically essential for biomedical applications.

Keywords

Melittin Peptitlerinin CD147 Reseptörü ile Etkileşimindeki Antikanser Potansiyeli: Ligand-Reseptör Etkileşiminin Yapısal ve Fonksiyonel Analizi

Öz

Bu araştırmada, antikanser etkileriyle bilinen melittin (MLT) peptitlerinin CD147 reseptörüyle etkileşimlerinin antikanser potansiyeli in silico yapısal ve işlevsel analizlerle araştırılmıştır. CD147 transmembran glikoproteini ve siklofilinA (CypA) etkileşimi, kanser patolojisinde önemli olan sinyal yollarını aktive eder. Bu çalışmada, melittin peptitlerinin bu etkileşimi engelleme potansiyeli üzerinde durulmuştur. CD147 reseptör yapısı ve melittin peptit yapıları Protein Veri Bankası'ndan (PDB) temin edilmiş olup; bunlar arasında CD147'nin Ig1 alanının üç boyutlu yapısı (PDB No: 5XF0) ve melittin yapıları (PDB No: 2MLT, 6O4M, 3QRX, 8AHT ve 8AHS) bulunmaktadır. PDB tarafından onaylanmış ligand yapıları X-ışını kırınımı ile elde edilmiştir. ClusPro2.0 moleküler bağlanma sunucusu, AnciCP2.0 ve ENNAACT antikanser analiz sunucuları, ProtScale hidrofobisite analiz, PDBSum aminoasit etkileşim analiz ve PRODIGY termodinamik stabilite analiz araçları kullanılarak reseptör-ligand etkileşimleri ve antikanser aktivite değerlendirildi. Moleküler bağlanma simülasyonları reseptör-ligand etkileşimlerini analiz etmiş ve hidrofobik etkileşimlerin rolünü vurgulamıştır. Yapısal analiz, peptit kalitesinde değişkenlikleri göstermiş; 2MLT olumlu özellikler sergilerken, 3QRX’in zayıf bütünlük gösterdiği tespit edilmiştir. Antikanser analiz sunucuları 5XF0 ve CD147/CypA ile benzer bağlanma desenleri sergileyen 2MLT ve 3QRX'in her ikisinin de potansiyel antikanser aktivitesi gösterebileceğini ortaya koymuştur. Özellikle 5XF0-2MLT kompleksindeki Gly181 ve Arg201 ile bağsız etkileşimler, 5XF0-3QRX kompleksindeki Pro180, Gly181 ve Arg201 ile bağsız etkileşimler çalışmamızda ortaya konularak CD147/CypA etkileşim şekline benzerliğine dikkat çekilmiştir. Bu nedenle, moleküler etkileşimlerin anlaşılması ve ilaç keşfini yönlendirmenin önemi, yapısal incelemeler ve hesaplamalı analizlerin vurgulanarak, bu komplekslerin antikanser etkileri ve ilaç tasarımı üzerindeki etkilerine dair bilgiler sunulmuştur; ayrıca, bu yapısal belirleyicilerin ve terapötik potansiyellerinin ileri araştırmaları, biyomedikal uygulamalar için kritik öneme sahiptir.

Anahtar Kelimeler

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Details

Primary Language

English

Subjects

Veterinary Sciences (Other)

Journal Section

Research Article

Authors

Barış Denk ^*
0000-0002-7586-0895
Türkiye

Early Pub Date

December 19, 2024

Publication Date

December 31, 2024

Submission Date

April 18, 2024

Acceptance Date

November 7, 2024

Published in Issue

Year 2024 Volume: 27 Number: Ek Sayı 2 (Suppl 2)

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1470524

IZ

https://izlik.org/JA48TH38EY

Cite

RIS / Bibtex

APA

Denk, B. (2024). Unveiling Anticancer Potential in the Interactions of Melittin Peptides with CD147 Receptor: A Structural and Functional Analysis of Ligand-Target Interactions. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(Ek Sayı 2 (Suppl 2), 287-297. https://doi.org/10.18016/ksutarimdoga.vi.1470524