View source for 7u9s


==Crystal structure of human D-amino acid oxidase in complex with inhibitor==
<StructureSection load='7u9s' size='340' side='right'caption='[[7u9s]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7u9s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7U9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U9S FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=M7I:5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,4-dihydropyrazine-2,3-dione'>M7I</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7u9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u9s OCA], [https://pdbe.org/7u9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u9s RCSB], [https://www.ebi.ac.uk/pdbsum/7u9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u9s ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OXDA_HUMAN 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.<ref>PMID:17303072</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:35482677</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7u9s" style="background-color:#fffaf0;"></div>

==See Also==
*[[Amino acid oxidase 3D structures|Amino acid oxidase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bell JA]]
[[Category: Skene RJ]]