3s68: Difference between revisions
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==Rat COMT in complex with SAM and Tolcapone at 1.85A, P3221, Rfree=22.0== | ==Rat COMT in complex with SAM and Tolcapone at 1.85A, P3221, Rfree=22.0== | ||
<StructureSection load='3s68' size='340' side='right' caption='[[3s68]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='3s68' size='340' side='right'caption='[[3s68]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3s68]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3s68]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S68 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TCW:TOLCAPONE'>TCW</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TCW:TOLCAPONE'>TCW</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3nwb|3nwb]], [[3r6t|3r6t]], [[3nwe|3nwe]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nwb|3nwb]], [[3r6t|3r6t]], [[3nwe|3nwe]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Comt ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Comt ([https://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'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Catechol_O-methyltransferase Catechol O-methyltransferase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3s68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s68 OCA], [https://pdbe.org/3s68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s68 RCSB], [https://www.ebi.ac.uk/pdbsum/3s68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s68 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/COMT_RAT 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3s68" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3s68" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Buffalo rat]] | [[Category: Buffalo rat]] | ||
[[Category: Catechol O-methyltransferase]] | [[Category: Catechol O-methyltransferase]] | ||
[[Category: Large Structures]] | |||
[[Category: Benz, J]] | [[Category: Benz, J]] | ||
[[Category: Ehler, A]] | [[Category: Ehler, A]] | ||
Revision as of 13:39, 22 June 2022
Rat COMT in complex with SAM and Tolcapone at 1.85A, P3221, Rfree=22.0Rat COMT in complex with SAM and Tolcapone at 1.85A, P3221, Rfree=22.0
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 PubMedThe biological activity of catechol neurotransmitters such as dopamine in the synapse is modulated by transporters and enzymes. Catechol-O-methyltransferase (COMT; EC 2.1.1.6) inactivates neurotransmitters by catalyzing the transfer of a methyl group from S-adenosylmethionine to catechols in the presence of Mg(2). This pathway also inactivates L-DOPA, the standard therapeutic for Parkinson's disease. Depletion of catechol neurotransmitters in the prefrontal cortex has been linked to schizophrenia. The inhibition of COMT therefore promises improvements in the treatment of these diseases. The concept of bisubstrate inhibitors for COMT has been described previously. Here, ribose-modified bisubstrate inhibitors were studied. Three high-resolution crystal structures of COMT in complex with novel ribose-modified bisubstrate inhibitors confirmed the predicted binding mode but displayed subtle alterations at the ribose-binding site. The high affinity of the inhibitors can be convincingly rationalized from the structures, which document the possibility of removing and/or replacing the ribose 3'-hydroxyl group and provide a framework for further inhibitor design. Catechol-O-methyltransferase in complex with substituted 3'-deoxyribose bisubstrate inhibitors.,Ellermann M, Lerner C, Burgy G, Ehler A, Bissantz C, Jakob-Roetne R, Paulini R, Allemann O, Tissot H, Grunstein D, Stihle M, Diederich F, Rudolph MG Acta Crystallogr D Biol Crystallogr. 2012 Mar;68(Pt 3):253-60. Epub 2012 Feb 14. PMID:22349227[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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