3w4j: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of human DAAO in complex with coumpound 12== | ==Crystal Structure of human DAAO in complex with coumpound 12== | ||
<StructureSection load='3w4j' size='340' side='right' caption='[[3w4j]], [[Resolution|resolution]] 2.74Å' scene=''> | <StructureSection load='3w4j' size='340' side='right'caption='[[3w4j]], [[Resolution|resolution]] 2.74Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3w4j]] is a 4 chain structure with sequence from [ | <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> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w4i|3w4i]], [[3w4k|3w4k]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DAO, DAMOX ([ | <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'>[ | <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'>[ | <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> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 3w4j" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3w4j" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Amino acid oxidase 3D structures|Amino acid oxidase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 27: | Line 30: | ||
[[Category: D-amino-acid oxidase]] | [[Category: D-amino-acid oxidase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Hamajima, T]] | [[Category: Hamajima, T]] | ||
[[Category: Harada, K]] | [[Category: Harada, K]] | ||
Revision as of 08:22, 3 August 2022
Crystal Structure of human DAAO in complex with coumpound 12Crystal Structure of human DAAO in complex with coumpound 12
Structural highlights
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] Publication Abstract from PubMedd-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. 4-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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||