3r6t: Difference between revisions

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<StructureSection load='3r6t' size='340' side='right'caption='[[3r6t]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
<StructureSection load='3r6t' size='340' side='right'caption='[[3r6t]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3r6t]] 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=3R6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R6T FirstGlance]. <br>
<table><tr><td colspan='2'>[[3r6t]] 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=3R6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R6T FirstGlance]. <br>
</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=DTD:DITHIANE+DIOL'>DTD</scene>, <scene name='pdbligand=LU1:4-FLUORO-4,5-DIHYDROXY-N-{(2E)-3-[(2S,4R,5R)-4-HYDROXY-5-(6-METHYL-9H-PURIN-9-YL)TETRAHYDROFURAN-2-YL]PROP-2-EN-1-YL}BIPHENYL-3-CARBOXAMIDE'>LU1</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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3u81|3u81]], [[3s68|3s68]], [[3nwb|3nwb]], [[3nwe|3nwe]]</div></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=DTD:DITHIANE+DIOL'>DTD</scene>, <scene name='pdbligand=LU1:4-FLUORO-4,5-DIHYDROXY-N-{(2E)-3-[(2S,4R,5R)-4-HYDROXY-5-(6-METHYL-9H-PURIN-9-YL)TETRAHYDROFURAN-2-YL]PROP-2-EN-1-YL}BIPHENYL-3-CARBOXAMIDE'>LU1</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>
<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'>[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'>[https://proteopedia.org/fgij/fg.htm?mol=3r6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6t OCA], [https://pdbe.org/3r6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r6t RCSB], [https://www.ebi.ac.uk/pdbsum/3r6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6t 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=3r6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r6t OCA], [https://pdbe.org/3r6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r6t RCSB], [https://www.ebi.ac.uk/pdbsum/3r6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r6t 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.  
[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;">
== Publication Abstract from PubMed ==
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.
 
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>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3r6t" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Catechol O-methyltransferase]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Benz, J]]
[[Category: Rattus norvegicus]]
[[Category: Ehler, A]]
[[Category: Benz J]]
[[Category: Rudolph, M G]]
[[Category: Ehler A]]
[[Category: Schlatter, D]]
[[Category: Rudolph MG]]
[[Category: Stihle, M]]
[[Category: Schlatter D]]
[[Category: Alternative initiation]]
[[Category: Stihle M]]
[[Category: Catecholamine metabolism]]
[[Category: Metal-binding]]
[[Category: Methyltransferase]]
[[Category: Neurotransmitter degradation]]
[[Category: S-adenosyl-l-methionine]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transmembrane]]

Latest revision as of 10:52, 21 February 2024

Rat catechol o-methyltransferase in complex with the bisubstrate inhibitor 4'-fluoro-4,5-dihydroxy-biphenyl-3-carboxylic acid {(E)-3-[(2S,4R,5R)-4-hydroxy-5-(6-methyl-purin-9-yl)-tetrahydro-furan-2-yl]-allyl}-amide

3r6t, resolution 1.20Å

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