4l1o

Crystal structure of human ALDH3A1 with inhibitor 1-{[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]methyl}-1H-indole-2,3-dioneCrystal structure of human ALDH3A1 with inhibitor 1-{[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]methyl}-1H-indole-2,3-dione

Structural highlights 4l1o is a 2 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 2.3Å Ligands: , , 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 Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and have been indicated to play a role in several cancerous disease states. Our laboratory is interested in developing novel and selective ALDH inhibitors. We looked to further work recently published by developing a class of isoenzyme-selective inhibitors using similar indole-2,3-diones that exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1. Kinetic and X-ray crystallography data suggest that these inhibitors are competitive against aldehyde binding, forming direct interactions with active-site cysteine residues. The selectivity is precise in that these compounds appear to interact directly with the catalytic nucleophile, Cys243, in ALDH3A1 but not in ALDH2. In ALDH2, the 3-keto group is surrounded by the adjacent Cys301/303. Surprisingly, the orientation of the interaction changes depending on the nature of the substitutions on the basic indole ring structure and correlates well with the observed structure-activity relationships for each ALDH isoenzyme. Development of selective inhibitors for aldehyde dehydrogenases based on substituted indole-2,3-diones.,Kimble-Hill AC, Parajuli B, Chen CH, Mochly-Rosen D, Hurley TD J Med Chem. 2014 Feb 13;57(3):714-22. doi: 10.1021/jm401377v. Epub 2014 Jan 31. PMID:24444054 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

spinqualitylabelsall models 4l1o, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image