title: Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1.
abstract: There is growing interest in aldehyde dehydrogenases (ALDHs) because of their overexpression in cancer stem cells and the ability to mediate resistance to cancer drugs. Here, we report the first crystal structure of an aldehyde dehydrogenase complexed with the inhibitor 4-diethylaminobenzaldehyde (DEAB). Contrary to the widely held belief that DEAB is a reversible inhibitor of ALDHs, we show that DEAB irreversibly inactivates ALDH7A1 via formation of a stable, covalent acyl-enzyme species.
authors.affiliation: †Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: †Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
authors.affiliation: ‡Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Henzl
authors.affiliation: †Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.|‡Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Tanner
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001547:Benzaldehydes / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D009243:NAD; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase