7u9s | pdb_00007u9s

Crystal structure of human D-amino acid oxidase in complex with inhibitor

spinqualitylabelsall models 7u9s, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7u9s 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 2.1Å Ligands: FAD, M7I Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OXDA_HUMAN Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids. Publication Abstract from PubMed d-Serine is a coagonist of the N-methyl d-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, d-serine is synthesized from its l-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO). Many studies have linked decreased d-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia. Thus, it is feasible to employ DAO inhibitors for the treatment of schizophrenia and other indications. Powered by the Schrodinger computational modeling platform, we initiated a research program to identify novel DAO inhibitors with the best-in-class properties. The program execution leveraged an hDAO FEP+ model to prospectively predict compound potency. A new class of DAO inhibitors with desirable properties has been discovered from this endeavor. Our modeling technology on this program has not only enhanced the efficiency of structure-activity relationship development but also helped to identify a previously unexplored subpocket for further optimization. Discovery of a Novel Class of d-Amino Acid Oxidase Inhibitors Using the Schrodinger Computational Platform.,Tang H, Jensen K, Houang E, McRobb FM, Bhat S, Svensson M, Bochevarov A, Day T, Dahlgren MK, Bell JA, Frye L, Skene RJ, Lewis JH, Osborne JD, Tierney JP, Gordon JA, Palomero MA, Gallati C, Chapman RSL, Jones DR, Hirst KL, Sephton M, Chauhan A, Sharpe A, Tardia P, Dechaux EA, Taylor A, Waddell RD, Valentine A, Janssens HB, Aziz O, Bloomfield DE, Ladha S, Fraser IJ, Ellard JM J Med Chem. 2022 May 12;65(9):6775-6802. doi: 10.1021/acs.jmedchem.2c00118. Epub , 2022 Apr 28. PMID:35482677 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Amino acid oxidase 3D structures

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