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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4pyq]] is a 2 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=4PYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PYQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[4pyq]] is a 2 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=4PYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PYQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2X1:4-({[3-(AMINOMETHYL)PHENYL]CARBAMOYL}AMINO)BENZENECARBOXIMIDAMIDE'>2X1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2X1:4-({[3-(AMINOMETHYL)PHENYL]CARBAMOYL}AMINO)BENZENECARBOXIMIDAMIDE'>2X1</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4pyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyq OCA], [https://pdbe.org/4pyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pyq RCSB], [https://www.ebi.ac.uk/pdbsum/4pyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyq 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=4pyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyq OCA], [https://pdbe.org/4pyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pyq RCSB], [https://www.ebi.ac.uk/pdbsum/4pyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyq 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 ==
Methylation catalysed by catechol-O-methyltransferase (COMT) is the main pathway of catechol neurotransmitter deactivation in the prefrontal cortex. Low levels of this class of neurotransmitters are held to be causative of diseases such as schizophrenia, depression and Parkinson's disease. Inhibition of COMT may increase neurotransmitter levels, thus offering a route for treatment. Structure-based drug design hitherto seems to be based on the closed enzyme conformation. Here, a set of apo, semi-holo, holo and Michaelis form crystal structures are described that define the conformational space available to COMT and that include likely intermediates along the catalytic pathway. Domain swaps and sizeable loop movements around the active site testify to the flexibility of this enzyme, rendering COMT a difficult drug target. The low affinity of the co-substrate S-adenosylmethionine and the large conformational changes involved during catalysis highlight significant energetic investment to achieve the closed conformation. Since each conformation of COMT is a bona fide target for inhibitors, other states than the closed conformation may be promising to address. Crystallographic data for an alternative avenue of COMT inhibition, i.e. locking of the apo state by an inhibitor, are presented. The set of COMT structures may prove to be useful for the development of novel classes of inhibitors.
Mapping the conformational space accessible to catechol-O-methyltransferase.,Ehler A, Benz J, Schlatter D, Rudolph MG Acta Crystallogr D Biol Crystallogr. 2014 Aug 1;70(Pt 8):2163-74. doi:, 10.1107/S1399004714012917. Epub 2014 Jul 25. PMID:25084335<ref>PMID:25084335</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pyq" 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/>
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__TOC__
</StructureSection>
</StructureSection>

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