| Autor: |
Tomić, Sanja, Kazazić, Saša, Abramić, Marija, Tomin, Marko, Agić, Dejan, Karačić, Zrinka, Grabar-Branilović, Marina |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Popis: |
We employed hydrogen/deuterium exchange reaction combined with molecular dynamics (MD) simulations to investigate conformational dynamics and ligand binding within the M49 enzyme family. Six, two- domain study dipeptidyl peptidase III (DPP III), orthologues, human, yeast, three bacterial and one moss were studies. According to the results all orthologues seems to be quite compact with protected regions located within the two domains core and with the overall flexibility profile consistent with semi-closed conformation as the dominant protein form in solution. Furthermore by comparing HDX data obtained for unliganded protein and its tynorphin complex it was found that tynorphin binds within the inter-domain cleft in all orthologues, but in different orientations. Docking combined with MD simulations revealed details of the protein ligand interactions on human, yeast and three bacterial DPPs III. H- bond analysis revealed that the interdomain active site cleft is more protected in the complexes than in apo enzyme and enabled interpretation of conformational changes noticed at regions distant from the binding site. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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