View source for 3znq


==IN VITRO AND IN VIVO INHIBITION OF HUMAN D-AMINO ACID OXIDASE: REGULATION OF D-SERINE CONCENTRATION IN THE BRAIN==
<StructureSection load='3znq' size='340' side='right'caption='[[3znq]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3znq]] 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=3ZNQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNQ 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]] 2.75&#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=SS8:3-PHENETHYL-4H-FURO[3,2-B]PYRROLE-5-CARBOXYLIC+ACID'>SS8</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=3znq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3znq OCA], [https://pdbe.org/3znq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3znq RCSB], [https://www.ebi.ac.uk/pdbsum/3znq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3znq 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 ==
We characterized the mechanism and pharmacodynamics of five structurally distinct inhibitors of d-amino acid oxidase. All inhibitors bound the oxidized form of human enzyme with affinity slightly higher than that of benzoate (Kd approximately 2-4 muM). Stopped-flow experiments showed that pyrrole-based inhibitors possessed high affinity (Kd approximately 100-200 nM) and slow release kinetics (k &lt; 0.01 s(-1)) in the presence of substrate, while inhibitors with pendent aromatic groups altered conformations of the active site lid, as evidenced by X-ray crystallography, and showed slower kinetics of association. Rigid bioisosteres of benzoic acid induced a closed-lid conformation, had slower release in the presence of substrate, and were more potent than benzoate. Steady-state d-serine concentrations were described in a PK/PD model, and competition for d-serine sites on NMDA receptors was demonstrated in vivo. DAAO inhibition increased the spatiotemporal influence of glial-derived d-serine, suggesting localized effects on neuronal circuits where DAAO can exert a neuromodulatory role.

Structural, Kinetic, and Pharmacodynamic Mechanisms of d-Amino Acid Oxidase Inhibition by Small Molecules.,Hopkins SC, Heffernan ML, Saraswat LD, Bowen CA, Melnick L, Hardy LW, Orsini MA, Allen MS, Koch P, Spear KL, Foglesong RJ, Soukri M, Chytil M, Fang QK, Jones SW, Varney MA, Panatier A, Oliet SH, Pollegioni L, Piubelli L, Molla G, Nardini M, Large TH J Med Chem. 2013 May 9;56(9):3710-24. doi: 10.1021/jm4002583. Epub 2013 Apr 30. PMID:23631755<ref>PMID:23631755</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3znq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Amino acid oxidase 3D structures|Amino acid oxidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allen MS]]
[[Category: Bowen CA]]
[[Category: Chytil M]]
[[Category: Fang QK]]
[[Category: Foglesong RJ]]
[[Category: Hardy LW]]
[[Category: Heffernan MLR]]
[[Category: Hopkins SC]]
[[Category: Jones SW]]
[[Category: Koch P]]
[[Category: Large TH]]
[[Category: Melnick L]]
[[Category: Molla G]]
[[Category: Nardini M]]
[[Category: Oliet SHR]]
[[Category: Orsini MA]]
[[Category: Panatier A]]
[[Category: Piubelli L]]
[[Category: Pollegioni L]]
[[Category: Saraswat LD]]
[[Category: Soukri M]]
[[Category: Spear KL]]
[[Category: Varney MA]]