4pyj - Revision history

OCA at 12:43, 1 March 2024

OCA — Fri, 01 Mar 2024 12:43:21 GMT

←Older revision		Revision as of 12:43, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PYJ 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.9Å</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=NA:SODIUM+ION'>NA</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [https://pdbe.org/4pyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [https://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj 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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [https://pdbe.org/4pyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [https://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/COMT_HUMAN COMT_HUMAN] 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_HUMAN COMT_HUMAN] 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4pyj" 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>

OCA at 07:37, 8 February 2023

OCA — Wed, 08 Feb 2023 07:37:14 GMT

←Older revision		Revision as of 07:37, 8 February 2023
Line 1:		Line 1:

	==human apo-COMT, single domain swap==		==human apo-COMT, single domain swap==
-	<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4pyj' size='340' side='right'caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PYJ 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=NA:SODIUM+ION'>NA</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=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [https://pdbe.org/4pyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [https://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj ProSAT]</span></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=9606 HUMAN])</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [~~http~~://pdbe.org/4pyj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/COMT_HUMAN COMT_HUMAN]] 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_HUMAN COMT_HUMAN] 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 ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4pyj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4pyj" 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: ~~Catechol O-methyltransferase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Benz, J]]	+	[[Category: Benz J]]
-	[[Category: Ehler, A]]	+	[[Category: Ehler A]]
-	[[Category: Rudolph~~, M G~~]]	+	[[Category: Rudolph MG]]
-	[[Category: Schlatter, D]]	+	[[Category: Schlatter D]]
-	~~[[Category: Catecholamine metabolism]]~~	+
-	~~[[Category: Cell membrane]]~~	+
-	~~[[Category: Conformational change]]~~	+
-	~~[[Category: Enzyme]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Neurotransmitter degradation]]~~	+
-	~~[[Category: Signal-anchor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:46, 22 November 2017

OCA — Wed, 22 Nov 2017 08:46:48 GMT

←Older revision		Revision as of 08:46, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYJ 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=NA:SODIUM+ION'>NA</scene></td></tr>		</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=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</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=9606 HUMAN])</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://pdbe.org/4pyj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj 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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://pdbe.org/4pyj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4pyj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4pyj" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Catechol O-methyltransferase\|Catechol O-methyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
		+	[[Category: Human]]
	[[Category: Benz, J]]		[[Category: Benz, J]]
	[[Category: Ehler, A]]		[[Category: Ehler, A]]

OCA at 11:09, 4 August 2016

OCA — Thu, 04 Aug 2016 11:09:32 GMT

←Older revision		Revision as of 11:09, 4 August 2016
Line 1:		Line 1:
		+
	==human apo-COMT, single domain swap==		==human apo-COMT, single domain swap==
	<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://pdbe.org/4pyj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pyj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4pyj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Catechol O-methyltransferase\|Catechol O-methyltransferase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:42, 25 December 2014

OCA — Thu, 25 Dec 2014 08:42:25 GMT

←Older revision		Revision as of 08:42, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>
-	</td></tr><tr><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=NA:SODIUM+ION'>NA</scene><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=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</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=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/COMT_HUMAN COMT_HUMAN]] 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 ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
-	[[Category: Benz, J.]]	+	[[Category: Benz, J]]
-	[[Category: Ehler, A.]]	+	[[Category: Ehler, A]]
-	[[Category: Rudolph, M G.]]	+	[[Category: Rudolph, M G]]
-	[[Category: Schlatter, D.]]	+	[[Category: Schlatter, D]]
	[[Category: Catecholamine metabolism]]		[[Category: Catecholamine metabolism]]
	[[Category: Cell membrane]]		[[Category: Cell membrane]]

OCA at 05:34, 27 August 2014

OCA — Wed, 27 Aug 2014 05:34:25 GMT

←Older revision		Revision as of 05:34, 27 August 2014
Line 8:		Line 8:
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</span></td></tr>		<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</span></td></tr>
	<table>		<table>
		+	<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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:58, 11 June 2014

OCA — Wed, 11 Jun 2014 08:58:08 GMT

←Older revision		Revision as of 08:58, 11 June 2014
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==human apo-COMT, single domain swap==
-		+	<StructureSection load='4pyj' size='340' side='right' caption='[[4pyj]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~The entry~~ 4pyj is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4pyj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PYJ FirstGlance]. <br>
-	~~Authors~~: ~~Ehler~~, A., ~~Benz~~, J., ~~Schlatter~~, D., Rudolph, M.G.	+	</td></tr><tr><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=NA:SODIUM+ION'>NA</scene><br>
-		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4p7k\|4p7k]], [[4p7f\|4p7f]], [[4p7g\|4p7g]], [[4p7j\|4p7j]], [[4pyi\|4pyi]], [[4pyk\|4pyk]], [[4pyl\|4pyl]], [[4pym\|4pym]], [[4pyn\|4pyn]]</td></tr>
-	~~Description~~: ~~human apo~~-~~COMT, single domain swap~~	+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pyj RCSB], [http://www.ebi.ac.uk/pdbsum/4pyj PDBsum]</span></td></tr>
		+	<table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Catechol O-methyltransferase]]
		+	[[Category: Benz, J.]]
		+	[[Category: Ehler, A.]]
		+	[[Category: Rudolph, M G.]]
		+	[[Category: Schlatter, D.]]
		+	[[Category: Catecholamine metabolism]]
		+	[[Category: Cell membrane]]
		+	[[Category: Conformational change]]
		+	[[Category: Enzyme]]
		+	[[Category: Membrane]]
		+	[[Category: Metal-binding]]
		+	[[Category: Methyltransferase]]
		+	[[Category: Neurotransmitter degradation]]
		+	[[Category: Signal-anchor]]
		+	[[Category: Transferase]]

OCA at 05:58, 9 April 2014

OCA — Wed, 09 Apr 2014 05:58:07 GMT

←Older revision		Revision as of 05:58, 9 April 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4pyj is ON HOLD	+	The entry 4pyj is ON HOLD until Paper Publication

-	Authors: ~~ehler~~, a., ~~benz~~, j., ~~schlatter~~, d., ~~rudolph~~, m.g.	+	Authors: Ehler, A., Benz, J., Schlatter, D., Rudolph, M.G.

	Description: human apo-COMT, single domain swap		Description: human apo-COMT, single domain swap

OCA: Protected "4pyj" [edit=sysop:move=sysop]

OCA — Wed, 02 Apr 2014 08:36:19 GMT

Protected "4pyj" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:36, 2 April 2014

OCA: New page: '''Unreleased structure''' The entry 4pyj is ON HOLD Authors: ehler, a., benz, j., schlatter, d., rudolph, m.g. Description: human apo-COMT, single domain swap

OCA — Wed, 02 Apr 2014 08:36:18 GMT

New page: '''Unreleased structure''' The entry 4pyj is ON HOLD Authors: ehler, a., benz, j., schlatter, d., rudolph, m.g. Description: human apo-COMT, single domain swap

New page

'''Unreleased structure'''

The entry 4pyj is ON HOLD

Authors: ehler, a., benz, j., schlatter, d., rudolph, m.g.

Description: human apo-COMT, single domain swap