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3nwe

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Current revision (10:01, 14 February 2024) (edit) (undo)
 
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<StructureSection load='3nwe' size='340' side='right'caption='[[3nwe]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='3nwe' size='340' side='right'caption='[[3nwe]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3nwe]] 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=3NWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NWE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3nwe]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NWE FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=662:5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-N-[(E)-3-[(2R,3R,4R,5R)-4-HYDROXY-3-METHYL-5-[6-(PROPYLAMINO)PURIN-9-YL]OXOLAN-2-YL]PROP-2-ENYL]BENZAMIDE'>662</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nw9|3nw9]], [[3nwb|3nwb]], [[3ozr|3ozr]], [[3ozs|3ozs]], [[3ozt|3ozt]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=662:5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-N-[(E)-3-[(2R,3R,4R,5R)-4-HYDROXY-3-METHYL-5-[6-(PROPYLAMINO)PURIN-9-YL]OXOLAN-2-YL]PROP-2-ENYL]BENZAMIDE'>662</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<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>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nwe OCA], [https://pdbe.org/3nwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nwe RCSB], [https://www.ebi.ac.uk/pdbsum/3nwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nwe ProSAT]</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=3nwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nwe OCA], [https://pdbe.org/3nwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nwe RCSB], [https://www.ebi.ac.uk/pdbsum/3nwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nwe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[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.
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The 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.
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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<ref>PMID:22349227</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3nwe" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Buffalo rat]]
 
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[[Category: Catechol O-methyltransferase]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Benz, J]]
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[[Category: Rattus norvegicus]]
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[[Category: Ehler, A]]
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[[Category: Benz J]]
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[[Category: Rudolph, M G]]
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[[Category: Ehler A]]
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[[Category: Schlatter, D]]
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[[Category: Rudolph MG]]
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[[Category: Stihle, M]]
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[[Category: Schlatter D]]
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[[Category: Alternative initiation]]
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[[Category: Stihle M]]
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[[Category: Catecholamine metabolism]]
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[[Category: Cell membrane]]
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[[Category: Magnesium]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Methyltransferase]]
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[[Category: Neurotransmitter degradation]]
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[[Category: Phosphoprotein]]
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[[Category: S-adenosyl-l-methionine]]
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[[Category: Signal-anchor]]
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[[Category: Transferase-transferase inhibitor complex]]
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[[Category: Transmembrane]]
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Current revision

Rat COMT in complex with a methylated desoxyribose bisubstrate-containing inhibitor avoids hydroxyl group

PDB ID 3nwe

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