6te5

Crystal structure of human Aldehyde dehydrogenase 1A3 in complex with LQ43 inhibitor compoundCrystal structure of human Aldehyde dehydrogenase 1A3 in complex with LQ43 inhibitor compound

Structural highlights 6te5 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 3.25Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease AL1A3_HUMAN Isolated anophthalmia - microphthalmia. The disease is caused by mutations affecting the gene represented in this entry. Function AL1A3_HUMAN Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity). Publication Abstract from PubMed Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It is known for its ability to escape the therapeutic options available to date thanks to the presence of a subset of cells endowed with stem-like properties and ability to resist to cytotoxic treatments. As the cytosolic enzyme aldehyde dehydrogenase 1A3 turns out to be overexpressed in these kinds of cells, playing a key role for their vitality, treatments targeting this enzyme may represent a successful strategy to fight GBM. In this work, we describe a novel class of imidazo[1,2-a]pyridine derivatives as aldehyde dehydrogenase 1A3 inhibitors, reporting the evidence of their significance as novel drug candidates for the treatment of GBM. Besides showing an interesting functional profile, in terms of activity against the target enzyme and selectivity toward highly homologous isoenzymes, representative examples of the series also showed a nanomolar to picomolar efficacy against patient-derived GBM stem-like cells, thus proving the concept that targeting aldehyde dehydrogenase might represent a novel and promising way to combat GBM by striking its ability to divide immortally. Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells.,Quattrini L, Gelardi ELM, Coviello V, Sartini S, Ferraris DM, Mori M, Nakano I, Garavaglia S, La Motta C J Med Chem. 2020 Apr 20. doi: 10.1021/acs.jmedchem.9b01910. PMID:32223240 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

spinqualitylabelsall models 6te5, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image