3w4j: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='3w4j' size='340' side='right'caption='[[3w4j]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3w4j]] 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=3W4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W4J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3w4j]] 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=3W4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W4J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2LD:3-HYDROXY-5-(2-PHENYLETHYL)PYRIDIN-2(1H)-ONE'>2LD</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 2.74&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3w4i|3w4i]], [[3w4k|3w4k]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2LD:3-HYDROXY-5-(2-PHENYLETHYL)PYRIDIN-2(1H)-ONE'>2LD</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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='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=3w4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w4j OCA], [https://pdbe.org/3w4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w4j RCSB], [https://www.ebi.ac.uk/pdbsum/3w4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w4j 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>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-d-Amino acid oxidase (DAAO) catalyzes the oxidation of d-amino acids including d-serine, a coagonist of the N-methyl-d-aspartate receptor. We identified a series of 4-hydroxypyridazin-3(2H)-one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment-based drug design. Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in-house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand-dependent manner. We investigated the ability of the initial fragment hit, 3-hydroxy-pyridine-2(1H)-one, to fill this subpocket with the aid of complex structure information. 3-Hydroxy-5-(2-phenylethyl)pyridine-2(1H)-one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme- and cell-based assays. We further designed and synthesized 4-hydroxypyridazin-3(2H)-one derivatives, which are equivalent to the 3-hydroxy-pyridine-2(1H)-one series but lack cell toxicity. 6-[2-(3,5-Difluorophenyl)ethyl]-4-hydroxypyridazin-3(2H)-one was found to be effective against MK-801-induced cognitive deficit in the Y-maze.
--Hydroxypyridazin-3(2H)-one Derivatives as Novel d-Amino Acid Oxidase Inhibitors.,Hondo T, Warizaya M, Niimi T, Namatame I, Yamaguchi T, Nakanishi K, Hamajima T, Harada K, Sakashita H, Matsumoto Y, Orita M, Takeuchi M J Med Chem. 2013 May 9;56(9):3582-92. doi: 10.1021/jm400095b. Epub 2013 Apr 25. PMID:23566269<ref>PMID:23566269</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3w4j" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 17: @@
 __TOC__
 </StructureSection>
-[[Category: D-amino-acid oxidase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Hamajima, T]]
+[[Category: Hamajima T]]
-[[Category: Harada, K]]
+[[Category: Harada K]]
-[[Category: Hondo, T]]
+[[Category: Hondo T]]
-[[Category: Matsumoto, Y]]
+[[Category: Matsumoto Y]]
-[[Category: Nakanishi, K]]
+[[Category: Nakanishi K]]
-[[Category: Namatame, I]]
+[[Category: Namatame I]]
-[[Category: Niimi, T]]
+[[Category: Niimi T]]
-[[Category: Orita, M]]
+[[Category: Orita M]]
-[[Category: Sakashita, H]]
+[[Category: Sakashita H]]
-[[Category: Takeuchi, M]]
+[[Category: Takeuchi M]]
-[[Category: Warizaya, M]]
+[[Category: Warizaya M]]
-[[Category: Watanabe, T]]
+[[Category: Watanabe T]]
-[[Category: Yamaguchi, T]]
+[[Category: Yamaguchi T]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]