Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1

  • ACS Chem Biol. 2015 Mar 20;10(3):693-7. doi: 10.1021/cb500977q.
Min Luo  1 ,  Kent S Gates  1 ,  Michael T Henzl  2 ,  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.

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