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4xuc

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Revision as of 01:49, 10 March 2017

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. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	4xud, 4xue
Activity:	Catechol O-methyltransferase, with EC number 2.1.1.6
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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT). ACS Med Chem Lett. 2015 Jan 26;6(3):318-23. doi: 10.1021/ml500502d. eCollection, 2015 Mar 12. PMID:25815153 doi:http://dx.doi.org/10.1021/ml500502d

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xuc"

@@ 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)==
 <StructureSection load='4xuc' size='340' side='right' caption='[[4xuc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xud|4xud]], [[4xue|4xue]]</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'>[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>
+<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://pdbe.org/4xuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xuc RCSB], [http://www.ebi.ac.uk/pdbsum/4xuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xuc ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4xuc" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4xuc

From Proteopedia

Revision as of 01:49, 10 March 2017

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

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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