3sz9

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3sz9, resolution 2.10Å ()
Ligands: , , ,
Gene: ALDH2, ALDM (Homo sapiens)
Activity: Aldehyde dehydrogenase (NAD(+)), with EC number 1.2.1.3
Related: 3sza, 3szb


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of human ALDH2 modified with the beta-elimination product of Aldi-3; 1-(4-ethylbenzene)prop-2-en-1-one

Publication Abstract from PubMed

Human aldehyde dehydrogenases (ALDH) comprise a family of seventeen homologous enzymes that metabolize different biogenic and exogenic aldehydes. To date, there are relatively few general ALDH inhibitors that can be used to probe the contribution of this class of enzymes to particular metabolic pathways. Here, we report the discovery of a general class of ALDH inhibitors with a common mechanism of action. The combined data from kinetic studies, mass spectrometric measurements and crystallographic analyses demonstrate that these novel inhibitors undergo an enzyme-mediated beta-elimination reaction generating a vinyl-ketone intermediate that covalently modifies the active site cysteine residue present in these enzymes. The studies described here can provide the basis for rational approach to design ALDH isoenzyme-specific inhibitors as research tools and perhaps as drugs, to address diseases, such as cancer, where increased ALDH activity is associated with cellular phenotype.

Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases., Khanna M, Chen CH, Kimble-Hill A, Parajuli B, Perez-Miller S, Baskaran S, Kim J, Dria K, Vasiliou V, Mochly-Rosen D, Hurley TD, J Biol Chem. 2011 Oct 21. PMID:22021038

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3sz9 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Khanna M, Chen CH, Kimble-Hill A, Parajuli B, Perez-Miller S, Baskaran S, Kim J, Dria K, Vasiliou V, Mochly-Rosen D, Hurley TD. Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases. J Biol Chem. 2011 Oct 21. PMID:22021038 doi:10.1074/jbc.M111.293597

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