3sza

Crystal structure of human ALDH3A1 - apo form

spinqualitylabelsall models 3sza, resolution 1.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3sza is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, K Related: 3sz9, 3szb Gene: ALDH3, ALDH3A1 (HUMAN) Activity: Aldehyde dehydrogenase (NAD(P)(+)), with EC number 1.2.1.5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AL3A1_HUMAN] ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes. 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.

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