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Information × Registration Number 0213U006717, 0108U008528 , R & D reports Title Study of the mechanism of interaction of 2',5'-oligoadenylates with calcium-binding proteins popup.stage_title Head Tkachuk Zenoviy Yuriyovich, Registration Date 25-12-2013 Organization Institute of molecular biology & genetics popup.description2 New methods of synthesis of drugs fluorescently labeled 2'- 5'- oligoadenylate and their analogues were designed. It is shown that the " core " 2'- 5'- oligoadenylates and their analogs can interact with calmodulin and change its binding with calcium. For all investigated drugs only activating activity were found. Modulating effect of 2'- 5'A3 and its analogs are relative to protein kinases. Titration curves of protein kinase depending on the oligoadenylate concentration has V- or W- shaped character. The model of the spatial structure of protein kinase C in the free state was build using computer simulation method and in silico dokynh number of ligands to this protein was performed. It is shown that 2'- 5'A3 bind in the active site of protein and form bonds with the protein. It is assumed that the 2'- 5'A3 and its analogues binding to regulatory proteins change their conformation , which leads to changes in their enzymatic activity . By mass spectroscopy method the ability of oligoadenylate ant its analogs to join to the proteins. These data provide an opportunity to examine ?- interferon as one of the target proteins for " core" oligoadenylate participating in the mechanism of antiviral cell deffence. Method CD spectroscopy showed that the inclusion of 2'- 5'- oligoadenylate analogs and their causes minor changes the three-dimensional structure of the protein globule, which served as a reflection of the decrease of the molar ellipticity . Analysis of the secondary structure of the protein S100A1 using the program CDNN has shown that adding oligoadenylate analogs led to a decrease in the percentage of ?- helical elements in the protein globule . We assume that oligoadenylate not interact directly with residues in interdomain interface , and mainly affect the surface homodimer after binding adenylats to Ca2 +- binding loop and / or areas of the linker. Experimental data obtained through the use of NMR and CD, indicating the occurrence of small changes in the structure of the protein as a result of interaction with the 2'-5'A3 and its analogues. Therefore, we believe that these compounds are able to regulate calcium affinity protein S100A1 and processes related to its interaction with target proteins. Analysis of FTIR spectra of the complexes of 2' -5 'A3 of calcium binding proteins S100A1, S100B and calmodulin showed the presence of the changing nature of absorption in the spectral regions corresponding to the Amide I and Amide II, which are known to be indicators of the state of the secondary structure of the protein globule . The above data directly indicate the presence of binding proteins studied with 2'-5'A3 and their influence on the conformation of the studied proteins. Keywords: 2'- 5'- oligoadenylate , calcium, calmodulin , protein S100A1, protein S100B, interferon, albumin, insulin.5481 Product Description popup.authors Дубей Ігор Ярославович Дубей Лариса Володимирівна Козлов Олександр вадимович Кузів Я. Б. Левченко Світлана Миколаївна Семерникова Лариса Іванівна Скоробагатов Олександр Ткачук Валентина Василівна Ткачук Зеновій Юрійович Ткачук Лариса Володимирівна Яковенко Тетяна Григорівна popup.nrat_date 2020-04-02 Close