5ac2

human aldehyde dehydrogenase 1A1 with duocarmycin analog

spinqualitylabelsall models 5ac2, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ac2 is a 1 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 1.85Å Ligands: K9P, TXE, YB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AL1A1_HUMAN Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity). Publication Abstract from PubMed Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial pi-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.,Koch MF, Harteis S, Blank ID, Pestel G, Tietze LF, Ochsenfeld C, Schneider S, Sieber SA Angew Chem Int Ed Engl. 2015 Sep 16. doi: 10.1002/anie.201505749. PMID:26373694 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

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