Detalhes
Nome
Marta VranasCargo
Técnico EspecialistaDesde
01 setembro 2023
Nacionalidade
PortugalServiço
Serviço de Apoio ao LicenciamentoContactos
+351222094000
marta.vranas@inesctec.pt
2022
Autores
Vranas, M; Lu, Y; Rasool, S; Croteau, N; Krett, JD; Sauvé, V; Gehring, K; Fon, EA; Durcan, TM; Trempe, J;
Publicação
Open Biology
Abstract
2021
Autores
Vranas, M; Wohlwend, D; Qiu, DY; Gerhardt, S; Trncik, C; Pervaiz, M; Ritter, K; Steimle, S; Randazzo, A; Einsle, O; Gunther, S; Jessen, HJ; Kotlyar, A; Friedrich, T;
Publicação
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Abstract
NADH:ubiquinone oxidoreductase, respiratory complex I, plays a central role in cellular energy metabolism. As a major source of reactive oxygen species (ROS) it affects ageing and mitochondrial dysfunction. The novel inhibitor NADH-OH specifically blocks NADH oxidation and ROS production by complex I in nanomolar concentrations. Attempts to elucidate its structure by NMR spectroscopy have failed. Here, by using X-ray crystallographic analysis, we report the structure of NADH-OH bound in the active site of a soluble fragment of complex I at 2.0 angstrom resolution. We have identified key amino acid residues that are specific and essential for binding NADH-OH. Furthermore, the structure sheds light on the specificity of NADH-OH towards the unique Rossmann-fold of complex I and indicates a regulatory role in mitochondrial ROS generation. In addition, NADH-OH acts as a lead-structure for the synthesis of a novel class of ROS suppressors.
2017
Autores
Tang, MY; Vranas, M; Krahn, AI; Pundlik, S; Trempe, JF; Fon, EA;
Publicação
Nature Communications
Abstract
2017
Autores
Dörner, K; Vranas, M; Schimpf, J; Straub, IR; Hoeser, J; Friedrich, T;
Publicação
Biochemistry
Abstract
2015
Autores
Sauvé, V; Lilov, A; Seirafi, M; Vranas, M; Rasool, S; Kozlov, G; Sprules, T; Wang, J; Trempe, J; Gehring, K;
Publicação
The EMBO Journal
Abstract
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