Agmatinin glutamaterjik iyon kanalları ile yapısal uygunluğunun araştırılması: Molecular docking çalışması

Öz

Amaç: Agmatin beynin hemen her yerinde eksprese olan ve modülatör olarak görev yaptığı düşünülen bir nörotransmiter olarak kabul görmektedir. Uyarılabilirlik ve aşırı uyarılabilirlik gibi fizyolojik ve patolojik durumlarla alakalı glutamaterjik iyon kanallarıyla etkileştiğine dair kanıtlar vardır. Bu çalışmada, nöbet ile ilişkili iyon kanallarının (KAR'lar, AMPAR'lar ve NMDAR'lar) agmatin ile olası ilişkileri moleküler docking yöntemi kullanılarak tartışılmaktadır. Gereç ve Yöntem: Glutamaterjik iyon kanallarına ait bilgiler Protein Data Banktan alındı. Kainat reseptörleri için 1YCJ, AMPA reseptörleri için 1FTM ve NMDA reseptörleri için 5EWJ kodlu protein XRD görüntüleri kullanıldı. Agmatin ve iyonotropik glutamat reseptör inhibitörleri olan topiramat, AMPA ve ifenprodilin 2D yapıları NCBI Pubchem 'den .sdf formatı olarak alındı. Auto Dock 4.2.6 yazılım programı kullanılarak simülasyon çalışmaları gerçekleştirildi. Bulgular: KAR, AMPA ve NMDA reseptörlerini sırasıyla bloke ettiği bilinen topiramat, AMPA ve ifenprodil için bağlanma bölgeleri ve bağlanma enerjileri belirlendi. Agmatinin bu reseptörlere bağlanma enerjisi referans moleküllerle kıyaslanarak verildi. Bu durumda agmatininKARlara bağlanma enerjisi -5.73 kkal/mol, AMPAlar için -5.41 kkal/mol ve son olarak NMDAlar için -4.01 kkal/mol olarak hesaplanmıştır. Ayrıca bu reseptörleri aktive ettiği bilinen glutamat molekülünün bağlanma enerjileri ile agmatin bağlanma enerjileri kıyaslandığında yakın enerji değerleri elde edilmiştir. Sonuç: Tüm bu değerlendirmeler göz önüne alındığında, Agmatinin sahip olduğu zayıf bağlar sonucu iyonotrofik glutamat reseptörleri AMPAR, KAR ve NMDAR'ı yapısal olarak bloke etme kabiliyetine sahip olmadığı söylenebilir. Bununla beraber glutamat bağlanmasına yakın bağlanma enerjileriyle kanala bağ kurma yeteneğine sahip gözükmektedir. Agmatinin reseptöre glutamat bağlama yerinden bağlandığını ancak reseptörü aktive etmek yerine glutamatın bağlanmasını bloke ederek reseptörün aktive olmasını engellemiş olabileceğini düşünüyoruz.

Anahtar Kelimeler

• Agmatin
• Uyarılabilirlik
• Moleküler yerleştirme çalışma

Investigation of structural suitability of agmatine with glutamatergic ion channels: Molecular docking study

Öz

Aim: Agmatine is considered a neurotransmitter that is expressed almost everywhere in the brain and is thought to act as a neuromodulator. There is evidence that it interacts with glutamatergic ion channels associated with physiological and pathological states such as excitability and hyperexcitability. In this study, possible relationships of seizure-related ion channels (KARs, AMPARs and NMDARs) with agmatine are discussed using molecular docking method. Material and Method: Information on glutamatergic ion channels was obtained from the Protein Data Bank. The 2D structure of agmatine and inhibitors of receptors were retrieved from NCBI PubChem in .sdf format. Simulation studies were carried out using the Auto Dock 4.2.6 software program. Results: Binding sites were determined. The binding energy of agmatine to these receptors was compared with reference molecules. In this case, the binding energy of agmatine to KAR, AMPAR and NMDARs is -5.73 kcal/mol, -5.41 kcal/mol and -4.01 kcal/mol, respectively. In addition, when compared with the binding energies of the glutamate molecule, approximate energy values were obtained. Conclusion: In conclusion, it can be said that Agmatine does not have the ability to structurally block the ionotrophic glutamate receptors AMPAR, KAR and NMDAR as a result of its weak bonds. However, it seems to have the ability to bond to the channel with binding energies close to glutamate binding. We think that agmatine binds to the receptor at the glutamate binding site, but instead of activating the receptor, it may have prevented the receptor from being activated by blocking the binding of glutamate.

Anahtar Kelimeler

• Agmatine
• Agmatine
• Excitability
• Molecular Docking study

Kaynakça

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