Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1

Min Luo; Kent S Gates; Michael T Henzl; John J Tanner

doi:10.1021/cb500977q

Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1

ACS Chem Biol. 2015 Mar 20;10(3):693-7. doi: 10.1021/cb500977q. Epub 2015 Jan 6.

Authors

Min Luo¹, Kent S Gates¹, Michael T Henzl², John J Tanner^{1

2}

Affiliations

¹ †Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.
² ‡Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211, United States.

PMID: 25554827
DOI: 10.1021/cb500977q

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aldehyde Dehydrogenase / antagonists & inhibitors*
Aldehyde Dehydrogenase / chemistry
Benzaldehydes / chemistry*
Binding Sites
Crystallography, X-Ray
Drug Discovery
Enzyme Inhibitors / chemistry*
Humans
Hydrogen Bonding
Models, Molecular
NAD / chemistry*
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary

Substances

Benzaldehydes
Enzyme Inhibitors
NAD
ALDH7A1 protein, human
Aldehyde Dehydrogenase