Proteīndisulfīdizomerāzes A17 izoformas strukturālie un funkcionālie pētījumi
Date
2020
Authors
Matisone, Sofija
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Bakalaura darba mērķis ir izpētīt PDI A17 (AGR2) izoformas strukturālās un funkcionālās īpašības, pro-onkogēno proteīndisulfīdu izomerāžu (PDI) selektīvo inhibitoru meklēšanas projekta ietvaros. Šīm nolūkam izstrādāt protokolu PDI A17 iegūšanai aktīvā formā, un piemērot proteīnu kodolu magnētiskās rezonanses (KMR) spektroskopijas pētīšanas metodei. Izpētīt saistību starp neaktivēto un aktivēto aziridīn-2-karbonskābes atvasinājumiem un PDI A17 izoformu. Šajā darbā aprakstīta optimizētas PDI A17 izoformas iegūšana, pamatoti izvēlētie apstākļi un metodes proteīna-ligandu saistības testēšanai ar 2D 1H-15N-HSQC eksperimenta palīdzību. Darbā arī ir aprakstīti pirmie rezultāti par aziridīn-2-karbonskābes N-sulfonil atvasinājumu saistības vietu PDI A17 aktīvajā centrā. Darbs izstrādāts Latvijas Organiskās sintēzes institūtā laika posmā no 2018. gada novembra līdz 2020. gada maijam.
The aim of bachelor’s theses is to study the structural and functional properties of PDI A17 (AGR2) isoform within the framework of a project of searching the selective inhibitors of pro-oncogenic protein disulfide isomerases (PDI). To fulfil the project, develop a protocol to obtain PDI A17 in its active form and adjust protein for studies by means of nuclear magnetic resonance (NMR) spectroscopy. Investigate the bind between non-activated and activated azidine- 2-carboxylic acid derivatives and PDI A17 isoform. This thesis describes the optimization of production of PDI A17 isoform, explains the choice of conditions and methods for protein-ligand binding studies by 2D 1H-15N-HSQC experiments. This work also illustrates the first results of binding of azidine-2-carboxylic acid N-sulfonyl derivatives to PDI A17 active site. The research was carried out in Latvian Institute of Organic Synthesis in the period from November 2018 to May 2020.
The aim of bachelor’s theses is to study the structural and functional properties of PDI A17 (AGR2) isoform within the framework of a project of searching the selective inhibitors of pro-oncogenic protein disulfide isomerases (PDI). To fulfil the project, develop a protocol to obtain PDI A17 in its active form and adjust protein for studies by means of nuclear magnetic resonance (NMR) spectroscopy. Investigate the bind between non-activated and activated azidine- 2-carboxylic acid derivatives and PDI A17 isoform. This thesis describes the optimization of production of PDI A17 isoform, explains the choice of conditions and methods for protein-ligand binding studies by 2D 1H-15N-HSQC experiments. This work also illustrates the first results of binding of azidine-2-carboxylic acid N-sulfonyl derivatives to PDI A17 active site. The research was carried out in Latvian Institute of Organic Synthesis in the period from November 2018 to May 2020.
Description
Keywords
Bioloģija , PDI A17 , AGR2 , KMR , 2D 1H-15N-HSQC , aziridīna cikls