Crystal structure and MD simulation of mouse EndoV reveal wedge motif plasticity in this inosine-specific endonuclease
| Autor: | Ingrun Alseth, Bjørn Dalhus, Pernille Blicher, Magnar Bjørås, Erik Sebastian Vik, Mia Elise Ronander, Anne Marthe Solvoll, Meh Sameen Nawaz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA repair Biology Molecular Dynamics Simulation Article 03 medical and health sciences chemistry.chemical_compound Endonuclease Deoxyribonuclease (Pyrimidine Dimer) Mice Hydrolase medicine Animals Humans Inosine Multidisciplinary 030102 biochemistry & molecular biology RNA 030104 developmental biology chemistry Biochemistry Nucleic acid biology.protein DNA medicine.drug |
| Zdroj: | Scientific Reports 'Scientific Reports ', vol: 6, pages: 24979-1-24979-11 (2016) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep24979 |
| Popis: | Endonuclease V (EndoV) is an enzyme with specificity for deaminated adenosine (inosine) in nucleic acids. EndoV from Escherichia coli (EcEndoV) acts both on inosines in DNA and RNA, whereas the human homolog cleaves only at inosines in RNA. Inosines in DNA are mutagenic and the role of EndoV in DNA repair is well established. In contrast, the biological function of EndoV in RNA processing is largely unexplored. Here we have characterized a second mammalian EndoV homolog, mouse EndoV (mEndoV) and show that mEndoV shares the same RNA selectivity as human EndoV (hEndoV). Mouse EndoV cleaves the same inosine-containing substrates as hEndoV, but with reduced efficiencies. The crystal structure of mEndoV reveals a conformation different from the hEndoV and prokaryotic EndoV structures, particularly for the conserved tyrosine in the wedge motif, suggesting that this strand separating element has some flexibility. Molecular dynamics simulations of mouse and human EndoV reveal alternative conformations for the invariant tyrosine. The configuration of the active site, on the other hand, is very similar between the prokaryotic and mammalian versions of EndoV. |
| Databáze: | OpenAIRE |
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