4xud
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4xud is ON HOLD Authors: Allison, T., Wolkenberg, S., Sanders, J.M., Soisson, S.M. Description: Synthesis and evaluation of heterocyclic catechol m...) |
|||
| (6 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd32 ([1-(biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid)== | |
| + | <StructureSection load='4xud' size='340' side='right'caption='[[4xud]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4xud]] is a 1 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=4XUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUD 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]] 2.4Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43H:[1-(BIPHENYL-3-YL)-5-HYDROXY-4-OXO-1,4-DIHYDROPYRIDIN-3-YL]BORONIC+ACID'>43H</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=4xud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xud OCA], [https://pdbe.org/4xud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xud RCSB], [https://www.ebi.ac.uk/pdbsum/4xud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xud ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/COMT_HUMAN COMT_HUMAN] Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg(2+). The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. | ||
| - | + | Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT).,Harrison ST, Poslusney MS, Mulhearn JJ, Zhao Z, Kett NR, Schubert JW, Melamed JY, Allison TJ, Patel SB, Sanders JM, Sharma S, Smith RF, Hall DL, Robinson RG, Sachs NA, Hutson PH, Wolkenberg SE, Barrow JC ACS Med Chem Lett. 2015 Jan 26;6(3):318-23. doi: 10.1021/ml500502d. eCollection, 2015 Mar 12. PMID:25815153<ref>PMID:25815153</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Allison | + | <div class="pdbe-citations 4xud" style="background-color:#fffaf0;"></div> |
| - | [[Category: Sanders | + | |
| - | [[Category: Soisson | + | ==See Also== |
| - | [[Category: Wolkenberg | + | *[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Allison T]] | ||
| + | [[Category: Sanders JM]] | ||
| + | [[Category: Soisson SM]] | ||
| + | [[Category: Wolkenberg S]] | ||
Current revision
Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd32 ([1-(biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid)
| |||||||||||
