Boğmaca toksini bağlamında adp ribozilasyon mekanızmasının kuramsal ve deneysel metotlarla incelenmesi
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Dosyalar
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
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Yayıncı
Trakya Üniversitesi, Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Boğmaca, akciğerler ve hava yollarında, özellikle bebekler ve çocuklarda yaygın şekilde görülen ve insan patojeni olarak Bordetella pertussis’in sebep olduğu yüksek bulaşıcılığa sahip bir bakteri enfeksiyonudur. Hastalık etkeni 133 kDa molekül ağırlığına sahip ve 5 alt birimden oluşan Pertussis Toksinidir. Hastalık etkeni olan Pertussis Toksin ADP-Ribozilleyen ölümcül bir toksin ailesine aittir. ADP-ribozilleyen toksinler; mono(ADPRT) önemli ilaç hedefli toksin ailesidir. Bu toksin ailesi NAD’ı katalizleyerek nikotinamid ve ADP-riboza ayrılmasını ve bu sayede ADPribozun hedef proteine transferini sağlar. ADP-ribozillenme proteinlerin özgün enzimler tarafından katalizlenmesi sonucu oluşan bir modifikasyondur. Bu mekanizma sayesinde, Pertussis Toksin, ADP-Ribozun eEF-2’ye transferini sağlar ve inhibe olan eEF-2 sayesinde protein sentezi durarak hücre ölümü gerçekleşir. Biz bu tez çalışmamızda Pertussis Toksininin NAD’a hangi bölgeden bağlandığını araştırdık. Çalışmamızın ileride bu konuda yapılacak olan başka inhibitör ve ilaç tasarım çalışmalarına katkıda bulunacağını düşünüyoruz.
Whooping cough, which is commonly seen especially in infants and children, is a highly contagious bacterial infection in the lungs and airways, caused by Bordetella pertussis known as a human pathogen. The cause of the disease is Pertussis Toxin which has a molecular weight of 133 kDa and consists of 5 subunits. Pertussis Toxin, the cause of the disease, belongs to a family of ADP-Ribozylating deadly toxins. ADP-ribosylating toxins; Mono (ADPRT) is an important drugtargeted toxin family. This toxin family catalyses NAD so as to separate nicotinamide and ADPribose; thereby it provides an opportunity for transferring ADP-ribose to the target protein. ADPribosylation is a modification becoming the result of catalyzed proteins by specific enzymes. Thanks to this mechanism Pertussis Toxin enables the transfer of ADP-Ribose to eEF-2 and protein synthesis stops and cell death occurs by means of inhibiting eEF-2. In this thesis we have investigated in which region Pertussis Toxin is bound to NAD. We believe that our study will contribute to further inhibitor and drug design studies in the future.
Whooping cough, which is commonly seen especially in infants and children, is a highly contagious bacterial infection in the lungs and airways, caused by Bordetella pertussis known as a human pathogen. The cause of the disease is Pertussis Toxin which has a molecular weight of 133 kDa and consists of 5 subunits. Pertussis Toxin, the cause of the disease, belongs to a family of ADP-Ribozylating deadly toxins. ADP-ribosylating toxins; Mono (ADPRT) is an important drugtargeted toxin family. This toxin family catalyses NAD so as to separate nicotinamide and ADPribose; thereby it provides an opportunity for transferring ADP-ribose to the target protein. ADPribosylation is a modification becoming the result of catalyzed proteins by specific enzymes. Thanks to this mechanism Pertussis Toxin enables the transfer of ADP-Ribose to eEF-2 and protein synthesis stops and cell death occurs by means of inhibiting eEF-2. In this thesis we have investigated in which region Pertussis Toxin is bound to NAD. We believe that our study will contribute to further inhibitor and drug design studies in the future.
Açıklama
Anahtar Kelimeler
Pertussis Toksin, eEF2, NAD, Protein Etkileşimi, ADP-Ribozillenme, Pertusis Toxin, Protein Interaction, ADP-Ribosylation
