2e48

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[[Image:2e48.gif|left|200px]]
 
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{{Structure
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==Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme==
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|PDB= 2e48 |SIZE=350|CAPTION= <scene name='initialview01'>2e48</scene>, resolution 2.90&Aring;
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<StructureSection load='2e48' size='340' side='right'caption='[[2e48]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene>
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<table><tr><td colspan='2'>[[2e48]] 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=2E48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E48 FirstGlance]. <br>
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|ACTIVITY= [http://en.wikipedia.org/wiki/D-amino-acid_oxidase D-amino-acid oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.3 1.4.3.3]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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|GENE=
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<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></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2e48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e48 OCA], [https://pdbe.org/2e48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e48 RCSB], [https://www.ebi.ac.uk/pdbsum/2e48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e48 ProSAT]</span></td></tr>
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</table>
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'''Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme'''
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== Function ==
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[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>
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/2e48_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e48 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
D-amino acid oxidase (DAO) degrades the gliotransmitter D-serine, a potent endogenous ligand of N-methyl-D-aspartate type glutamate receptors. It also has been suggested that D-DOPA, the stereoisomer of L-DOPA, is oxidized by DAO and then converted to dopamine via an alternative biosynthetic pathway. Here, we provide direct crystallographic evidence that D-DOPA is readily fitted into the active site of human DAO, where it is oxidized by the enzyme. Moreover, our kinetic data show that the maximal velocity for oxidation of D-DOPA is much greater than for D-serine, which strongly supports the proposed alternative pathway for dopamine biosynthesis in the treatment of Parkinson's disease. In addition, determination of the structures of human DAO in various states revealed that the conformation of the hydrophobic VAAGL stretch (residues 47-51) to be uniquely stable in the human enzyme, which provides a structural basis for the unique kinetic features of human DAO.
D-amino acid oxidase (DAO) degrades the gliotransmitter D-serine, a potent endogenous ligand of N-methyl-D-aspartate type glutamate receptors. It also has been suggested that D-DOPA, the stereoisomer of L-DOPA, is oxidized by DAO and then converted to dopamine via an alternative biosynthetic pathway. Here, we provide direct crystallographic evidence that D-DOPA is readily fitted into the active site of human DAO, where it is oxidized by the enzyme. Moreover, our kinetic data show that the maximal velocity for oxidation of D-DOPA is much greater than for D-serine, which strongly supports the proposed alternative pathway for dopamine biosynthesis in the treatment of Parkinson's disease. In addition, determination of the structures of human DAO in various states revealed that the conformation of the hydrophobic VAAGL stretch (residues 47-51) to be uniquely stable in the human enzyme, which provides a structural basis for the unique kinetic features of human DAO.
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==Disease==
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Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis.,Kawazoe T, Tsuge H, Imagawa T, Aki K, Kuramitsu S, Fukui K Biochem Biophys Res Commun. 2007 Apr 6;355(2):385-91. Epub 2007 Feb 8. PMID:17303072<ref>PMID:17303072</ref>
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Known diseases associated with this structure: Schizophrenia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124050 124050]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2E48 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E48 OCA].
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</div>
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<div class="pdbe-citations 2e48" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis., Kawazoe T, Tsuge H, Imagawa T, Aki K, Kuramitsu S, Fukui K, Biochem Biophys Res Commun. 2007 Apr 6;355(2):385-91. Epub 2007 Feb 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17303072 17303072]
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*[[Amino acid oxidase 3D structures|Amino acid oxidase 3D structures]]
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[[Category: D-amino-acid oxidase]]
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*[[Rossmann fold|Rossmann fold]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Fukui, K.]]
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[[Category: Fukui K]]
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[[Category: Imagawa, T.]]
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[[Category: Imagawa T]]
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[[Category: Kawazoe, T.]]
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[[Category: Kawazoe T]]
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[[Category: Tsuge, H.]]
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[[Category: Tsuge H]]
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[[Category: FAD]]
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[[Category: structurally ambivalent peptide]]
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[[Category: substrate-free holoenzyme]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:35:08 2008''
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Current revision

Crystal Structure of Human D-Amino Acid Oxidase: Substrate-Free Holoenzyme

PDB ID 2e48

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