Titel
Inhibitors of Fumarylacetoacetate Hydrolase Domain Containing Protein 1 (FAHD1)
Autor*in
Alexander K. H. Weiss
Research Institute for Biomedical Aging Research, University of Innsbruck
Patrycia Klapec
University of Applied Sciences Wiener Neustadt
... show all
Abstract
FAH domain containing protein 1 (FAHD1) acts as oxaloacetate decarboxylase in mitochondria, contributing to the regulation of the tricarboxylic acid cycle. Guided by a high-resolution X-ray structure of FAHD1 liganded by oxalate, the enzymatic mechanism of substrate processing is analyzed in detail. Taking the chemical features of the FAHD1 substrate oxaloacetate into account, the potential inhibitor structures are deduced. The synthesis of drug-like scaffolds afforded first-generation FAHD1-inhibitors with activities in the low micromolar IC50 range. The investigations disclosed structures competing with the substrate for binding to the metal cofactor, as well as scaffolds, which may have a novel binding mode to FAHD1.
Stichwort
FAHD1enzyme inhibitormitochondriaODxoxaloacetate
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:1604016
Erschienen in
Titel
Molecules
Band
26
Ausgabe
16
ISSN
1420-3049
Erscheinungsdatum
2021
Publication
MDPI AG
Erscheinungsdatum
2021
Zugänglichkeit
Rechte
Rechteangabe
© 2021 by the authors
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