4xuc: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(3 intermediate revisions by the same user not shown)
Line 1: Line 1:
==Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)==
==Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)==
<StructureSection load='4xuc' size='340' side='right' caption='[[4xuc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='4xuc' size='340' side='right'caption='[[4xuc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4xuc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XUC FirstGlance]. <br>
<table><tr><td colspan='2'>[[4xuc]] 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=4XUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=43G:1-(BIPHENYL-3-YL)-3-HYDROXYPYRIDIN-4(1H)-ONE'>43G</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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xud|4xud]], [[4xue|4xue]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43G:1-(BIPHENYL-3-YL)-3-HYDROXYPYRIDIN-4(1H)-ONE'>43G</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catechol_O-methyltransferase Catechol O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.6 2.1.1.6] </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=4xuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xuc OCA], [https://pdbe.org/4xuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xuc RCSB], [https://www.ebi.ac.uk/pdbsum/4xuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xuc ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xuc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xuc RCSB], [http://www.ebi.ac.uk/pdbsum/4xuc PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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.  
[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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Catechol O-methyltransferase]]
[[Category: Homo sapiens]]
[[Category: Allison, T]]
[[Category: Large Structures]]
[[Category: Sanders, J M]]
[[Category: Allison T]]
[[Category: Soisson, S M]]
[[Category: Sanders JM]]
[[Category: Wolkenberg, S]]
[[Category: Soisson SM]]
[[Category: Catechol-o-methyltransferase]]
[[Category: Wolkenberg S]]
[[Category: Comt]]

Latest revision as of 16:01, 1 March 2024

Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)

Structural highlights

4xuc is a 1 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 1.8Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

See Also

4xuc, resolution 1.80Å

Drag the structure with the mouse to rotate

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

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=4xuc&oldid=4076678"