3sz9

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

spinqualitylabelsall models 3sz9, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3sz9 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: EDO, GAI, I3E, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALDH2_HUMAN 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. See Also Aldehyde dehydrogenase 3D structures

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