3G3E
Crystal structure of human D-amino acid oxidase in complex with hydroxyquinolin-2(1H)
Summary for 3G3E
| Entry DOI | 10.2210/pdb3g3e/pdb |
| Descriptor | D-amino-acid oxidase, FLAVIN-ADENINE DINUCLEOTIDE, 3-hydroxyquinolin-2(1H)-one, ... (4 entities in total) |
| Functional Keywords | d-amino acid oxidase, fad, flavoprotein, oxidoreductase, peroxisome |
| Biological source | Homo sapiens (human) |
| Cellular location | Peroxisome: P14920 |
| Total number of polymer chains | 4 |
| Total formula weight | 163736.84 |
| Authors | Duplantier, A.,Liu, S. (deposition date: 2009-02-02, release date: 2009-06-23, Last modification date: 2023-09-06) |
| Primary citation | Duplantier, A.J.,Becker, S.L.,Bohanon, M.J.,Borzilleri, K.A.,Chrunyk, B.A.,Downs, J.T.,Hu, L.Y.,El-Kattan, A.,James, L.C.,Liu, S.,Lu, J.,Maklad, N.,Mansour, M.N.,Mente, S.,Piotrowski, M.A.,Sakya, S.M.,Sheehan, S.,Steyn, S.J.,Strick, C.A.,Williams, V.A.,Zhang, L. Discovery, SAR, and pharmacokinetics of a novel 3-Hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors J.Med.Chem., 52:3576-3585, 2009 Cited by PubMed Abstract: 3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystallization of 2 with the human DAAO enzyme defined the binding site and guided the design of new analogues. The SAR, pharmacokinetics, brain exposure, and effects on cerebellum D-serine are described. Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR versus the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine. PubMed: 19438227DOI: 10.1021/jm900128w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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