3nw9 - Revision history

OCA at 10:01, 14 February 2024

OCA — Wed, 14 Feb 2024 10:01:37 GMT

←Older revision		Revision as of 10:01, 14 February 2024
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	<StructureSection load='3nw9' size='340' side='right'caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='3nw9' size='340' side='right'caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3nw9]] 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=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3nw9]] 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=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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~~></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]] 1.65Å</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]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [https://pdbe.org/3nw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [https://www.ebi.ac.uk/pdbsum/3nw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nw9 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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [https://pdbe.org/3nw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [https://www.ebi.ac.uk/pdbsum/3nw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nw9 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 ==~~	+
-	L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbruggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC(50) values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg(2+) confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group.	+
-		+
-	Molecular recognition at the active site of catechol-O-methyltransferase (COMT): adenine replacements in bisubstrate inhibitors.,Ellermann M, Paulini R, Jakob-Roetne R, Lerner C, Borroni E, Roth D, Ehler A, Schweizer WB, Schlatter D, Rudolph MG, Diederich F Chemistry. 2011 May 27;17(23):6369-81. doi: 10.1002/chem.201003648. Epub, 2011 Apr 27. PMID:21538606<ref>PMID:21538606</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3nw9" 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: Cell membrane]]~~	+
-	~~[[Category: Magnesium]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Neurotransmitter degradation]]~~	+
-	~~[[Category: S-adenosyl-l-methionine]]~~	+
-	~~[[Category: Signal-anchor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:10, 12 May 2022

OCA — Thu, 12 May 2022 07:10:27 GMT

←Older revision		Revision as of 07:10, 12 May 2022
Line 1:		Line 1:

	==Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor==		==Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor==
-	<StructureSection load='3nw9' size='340' side='right' caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='3nw9' size='340' side='right'caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3nw9]] 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=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</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]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</div></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=10116 Buffalo rat])</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'>[~~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'>[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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [~~http~~://pdbe.org/3nw9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3nw9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3nw9 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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [https://pdbe.org/3nw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [https://www.ebi.ac.uk/pdbsum/3nw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nw9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3nw9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3nw9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Catechol O-methyltransferase 3D structures\|Catechol O-methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	[[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]]

OCA at 08:36, 8 November 2017

OCA — Wed, 08 Nov 2017 08:36:17 GMT

←Older revision		Revision as of 08:36, 8 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3nw9" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3nw9" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Catechol O-methyltransferase\|Catechol O-methyltransferase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:43, 4 August 2016

OCA — Thu, 04 Aug 2016 11:43:20 GMT

←Older revision		Revision as of 11:43, 4 August 2016
Line 1:		Line 1:
		+
	==Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor==		==Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor==
	<StructureSection load='3nw9' size='340' side='right' caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='3nw9' size='340' side='right' caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</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=10116 ~~Rattus norvegicus~~])</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=10116 Buffalo rat])</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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nw9 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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [http://pdbe.org/3nw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nw9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 3nw9" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
-	[[Category: Rattus norvegicus]]
	[[Category: Benz, J]]		[[Category: Benz, J]]
	[[Category: Ehler, A]]		[[Category: Ehler, A]]

OCA at 08:58, 25 December 2014

OCA — Thu, 25 Dec 2014 08:58:13 GMT

←Older revision		Revision as of 08:58, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</td></tr>
-	<tr><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=10116 Rattus norvegicus])</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=10116 Rattus norvegicus])</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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nw9 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=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nw9 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://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 ==
Line 15:		Line 17:
	Molecular recognition at the active site of catechol-O-methyltransferase (COMT): adenine replacements in bisubstrate inhibitors.,Ellermann M, Paulini R, Jakob-Roetne R, Lerner C, Borroni E, Roth D, Ehler A, Schweizer WB, Schlatter D, Rudolph MG, Diederich F Chemistry. 2011 May 27;17(23):6369-81. doi: 10.1002/chem.201003648. Epub, 2011 Apr 27. PMID:21538606<ref>PMID:21538606</ref>		Molecular recognition at the active site of catechol-O-methyltransferase (COMT): adenine replacements in bisubstrate inhibitors.,Ellermann M, Paulini R, Jakob-Roetne R, Lerner C, Borroni E, Roth D, Ehler A, Schweizer WB, Schlatter D, Rudolph MG, Diederich F Chemistry. 2011 May 27;17(23):6369-81. doi: 10.1002/chem.201003648. Epub, 2011 Apr 27. PMID:21538606<ref>PMID:21538606</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
		+
		+	==See Also==
		+	*[[Catechol O-methyltransferase\|Catechol O-methyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
Line 23:		Line 28:
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
-	[[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: Stihle, M.]]	+	[[Category: Stihle, M]]
	[[Category: Alternative initiation]]		[[Category: Alternative initiation]]
	[[Category: Catecholamine metabolism]]		[[Category: Catecholamine metabolism]]

OCA at 10:33, 28 May 2014

OCA — Wed, 28 May 2014 10:33:13 GMT

←Older revision		Revision as of 10:33, 28 May 2014
Line 1:		Line 1:
-	[[~~Image:~~3nw9.~~png~~\|~~left~~\|~~200px~~]]	+	==Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor==
		+	<StructureSection load='3nw9' size='340' side='right' caption='[[3nw9]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NW9 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=637:N-[(E)-3-[(2R,3S,4R,5R)-3,4-DIHYDROXY-5-(6-METHYLPURIN-9-YL)OXOLAN-2-YL]PROP-2-ENYL]-5-(4-FLUOROPHENYL)-2,3-DIHYDROXY-BENZAMIDE'>637</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><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nwb\|3nwb]], [[3nwe\|3nwe]], [[3ozr\|3ozr]], [[3ozs\|3ozs]], [[3ozt\|3ozt]]</td></tr>
		+	<tr><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=10116 Rattus norvegicus])</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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nw9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nw9 RCSB], [http://www.ebi.ac.uk/pdbsum/3nw9 PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbruggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC(50) values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg(2+) confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group.

-	<!--	+	Molecular recognition at the active site of catechol-O-methyltransferase (COMT): adenine replacements in bisubstrate inhibitors.,Ellermann M, Paulini R, Jakob-Roetne R, Lerner C, Borroni E, Roth D, Ehler A, Schweizer WB, Schlatter D, Rudolph MG, Diederich F Chemistry. 2011 May 27;17(23):6369-81. doi: 10.1002/chem.201003648. Epub, 2011 Apr 27. PMID:21538606<ref>PMID:21538606</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3nw9"~~, ~~creates the "Structure Box" on the page~~.	+
-	~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded~~),	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3nw9\| PDB=3nw9 \| SCENE= }}~~	+

-	~~===Rat COMT in complex with~~ a ~~methylpurin-containing bisubstrate inhibitor===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-		+	== References ==
-	~~<!--~~	+	<references/>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21538606}}, adds~~ the ~~Publication Abstract to the page~~	+	__TOC__
-	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 21538606 is the PubMed ID number~~.	+	</StructureSection>
-	-->	+
-	~~{{ABSTRACT_PUBMED_21538606}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3nw9]] is a 1 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA].~~	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:021538606<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]

OCA at 05:21, 23 May 2012

OCA — Wed, 23 May 2012 05:21:34 GMT

←Older revision		Revision as of 05:21, 23 May 2012
Line 11:		Line 11:
	===Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor===		===Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21538606}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21538606 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21538606}}

	==About this Structure==		==About this Structure==
Line 19:		Line 25:
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
		+	[[Category: Benz, J.]]
		+	[[Category: Ehler, A.]]
	[[Category: Rudolph, M G.]]		[[Category: Rudolph, M G.]]
		+	[[Category: Schlatter, D.]]
		+	[[Category: Stihle, M.]]
		+	[[Category: Alternative initiation]]
		+	[[Category: Catecholamine metabolism]]
		+	[[Category: Cell membrane]]
		+	[[Category: Magnesium]]
		+	[[Category: Membrane]]
		+	[[Category: Metal-binding]]
		+	[[Category: Methyltransferase]]
		+	[[Category: Neurotransmitter degradation]]
		+	[[Category: S-adenosyl-l-methionine]]
		+	[[Category: Signal-anchor]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 04:55, 1 June 2011

OCA — Wed, 01 Jun 2011 04:55:38 GMT

←Older revision		Revision as of 04:55, 1 June 2011
Line 1:		Line 1:
-	[[Image:3nw9.~~jpg~~\|left\|200px]]	+	[[Image:3nw9.png\|left\|200px]]

	<!--		<!--
Line 14:		Line 14:
	==About this Structure==		==About this Structure==
	[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA].		[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021538606</ref><references group="xtra"/>
	[[Category: Catechol O-methyltransferase]]		[[Category: Catechol O-methyltransferase]]
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Rudolph, M G.]]		[[Category: Rudolph, M G.]]

OCA: Protected "3nw9" [edit=sysop:move=sysop]

OCA — Wed, 16 Mar 2011 08:33:03 GMT

Protected "3nw9" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:33, 16 March 2011

OCA at 08:32, 16 March 2011

OCA — Wed, 16 Mar 2011 08:32:58 GMT

←Older revision		Revision as of 08:32, 16 March 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3nw9.jpg\|left\|200px]]

-	The ~~entry 3nw9~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3nw9", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3nw9\| PDB=3nw9 \| SCENE= }}

-	~~Authors: Rudolph, M.G.~~	+	===Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor===

-	Description: Rat COMT in complex with a methylpurin-containing bisubstrate inhibitor

-	~~''Page seeded by~~ [http://oca.weizmann.ac.il/oca OCA ] ~~on Wed Aug 25 08~~:36:~~34 2010''~~	+	==About this Structure==
		+	[[3nw9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NW9 OCA].
		+	[[Category: Catechol O-methyltransferase]]
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Rudolph, M G.]]