3g3e

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human D-amino acid oxidase in complex with hydroxyquinolin-2(1H)

Structural highlights

3g3e is a 4 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 2.2Å
Ligands:	,
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.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Discovery, SAR, and pharmacokinetics of a novel 3-Hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors.,Duplantier AJ, Becker SL, Bohanon MJ, Borzilleri KA, Chrunyk BA, Downs JT, Hu LY, El-Kattan A, James LC, Liu S, Lu J, Maklad N, Mansour MN, Mente S, Piotrowski MA, Sakya SM, Sheehan S, Steyn SJ, Strick CA, Williams VA, Zhang L J Med Chem. 2009 Jun 11;52(11):3576-85. PMID:19438227^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kawazoe T, Tsuge H, Imagawa T, Aki K, Kuramitsu S, Fukui K. Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis. Biochem Biophys Res Commun. 2007 Apr 6;355(2):385-91. Epub 2007 Feb 8. PMID:17303072 doi:10.1016/j.bbrc.2007.01.181
↑ Duplantier AJ, Becker SL, Bohanon MJ, Borzilleri KA, Chrunyk BA, Downs JT, Hu LY, El-Kattan A, James LC, Liu S, Lu J, Maklad N, Mansour MN, Mente S, Piotrowski MA, Sakya SM, Sheehan S, Steyn SJ, Strick CA, Williams VA, 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. 2009 Jun 11;52(11):3576-85. PMID:19438227 doi:10.1021/jm900128w

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3g3e"

Categories: Homo sapiens | Large Structures | Duplantier A | Liu S

@@ Line 3: / Line 3: @@
 <StructureSection load='3g3e' size='340' side='right'caption='[[3g3e]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3g3e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G3E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3g3e]] is a 4 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=3G3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G3E FirstGlance]. <br>
-</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=G3E:3-HYDROXYQUINOLIN-2(1H)-ONE'>G3E</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DAO, DAMOX ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=G3E:3-HYDROXYQUINOLIN-2(1H)-ONE'>G3E</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/D-amino-acid_oxidase D-amino-acid oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.3 1.4.3.3] </span></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=3g3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g3e OCA], [https://pdbe.org/3g3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g3e RCSB], [https://www.ebi.ac.uk/pdbsum/3g3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g3e 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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: D-amino-acid oxidase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Duplantier, A]]
+[[Category: Duplantier A]]
-[[Category: Liu, S]]
+[[Category: Liu S]]
-[[Category: D-amino acid oxidase]]
-[[Category: Fad]]
-[[Category: Flavoprotein]]
-[[Category: Oxidoreductase]]
-[[Category: Peroxisome]]

3g3e

From Proteopedia

Current revision

Crystal structure of human D-amino acid oxidase in complex with hydroxyquinolin-2(1H)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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