5k0f: Difference between revisions
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==Crystal Structure of COMT in complex with 5-[5-[1-(4-methoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2,4-dimethyl-1,3-thiazole== | ==Crystal Structure of COMT in complex with 5-[5-[1-(4-methoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2,4-dimethyl-1,3-thiazole== | ||
<StructureSection load='5k0f' size='340' side='right' caption='[[5k0f]], [[Resolution|resolution]] 1.81Å' scene=''> | <StructureSection load='5k0f' size='340' side='right'caption='[[5k0f]], [[Resolution|resolution]] 1.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5k0f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K0F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K0F FirstGlance]. <br> | <table><tr><td colspan='2'>[[5k0f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K0F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K0F FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6P1:5-{3-[(1R)-1-(4-METHOXYPHENYL)ETHYL]-1H-PYRAZOL-5-YL}-2,4-DIMETHYL-1,3-THIAZOLE'>6P1</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6P1:5-{3-[(1R)-1-(4-METHOXYPHENYL)ETHYL]-1H-PYRAZOL-5-YL}-2,4-DIMETHYL-1,3-THIAZOLE'>6P1</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Comt ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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='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=5k0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k0f OCA], [http://pdbe.org/5k0f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k0f RCSB], [http://www.ebi.ac.uk/pdbsum/5k0f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k0f 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=5k0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k0f OCA], [http://pdbe.org/5k0f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k0f RCSB], [http://www.ebi.ac.uk/pdbsum/5k0f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k0f ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5k0f" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5k0f" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | |||
[[Category: Catechol O-methyltransferase]] | [[Category: Catechol O-methyltransferase]] | ||
[[Category: Large Structures]] | |||
[[Category: Ehler, A]] | [[Category: Ehler, A]] | ||
[[Category: | [[Category: Rodriguez-Sarmiento, R M]] | ||
[[Category: Rudolph, M G]] | [[Category: Rudolph, M G]] | ||
[[Category: Catechol]] | [[Category: Catechol]] | ||
Revision as of 09:00, 12 June 2019
Crystal Structure of COMT in complex with 5-[5-[1-(4-methoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2,4-dimethyl-1,3-thiazoleCrystal Structure of COMT in complex with 5-[5-[1-(4-methoxyphenyl)ethyl]-1H-pyrazol-3-yl]-2,4-dimethyl-1,3-thiazole
Structural highlights
Function[COMT_RAT] 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 PubMedA fragment screening approach designed to target specifically the S-adenosyl-l-methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X-ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported. These compounds represent a novel series of potent COMT inhibitors that might be further optimized to new drugs useful for the treatment of Parkinson's disease, as adjuncts in levodopa based therapy, or for the treatment of schizophrenia. Design of Potent and Druglike Nonphenolic Inhibitors for Catechol O-Methyltransferase Derived from a Fragment Screening Approach Targeting the S-Adenosyl-l-methionine Pocket.,Lerner C, Jakob-Roetne R, Buettelmann B, Ehler A, Rudolph M, Rodriguez Sarmiento RM J Med Chem. 2016 Oct 14. PMID:27685665[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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