1h1d: Difference between revisions

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-[[Image:1h1d.png|left|200px]]
-{{STRUCTURE_1h1d|  PDB=1h1d  |  SCENE=  }}
+==Catechol O-Methyltransferase==
+<StructureSection load='1h1d' size='340' side='right'caption='[[1h1d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1h1d]] 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=1H1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H1D FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BIA:1-(3,4,DIHYDROXY-5-NITROPHENYL)-3-{4-[3-(TRIFLUOROMETHYL)+PHENYL]+PIPERAZIN-1-YL}PROPAN-1-ONE'>BIA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=1h1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h1d OCA], [https://pdbe.org/1h1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h1d RCSB], [https://www.ebi.ac.uk/pdbsum/1h1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h1d ProSAT]</span></td></tr>
+</table>
+== 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h1/1h1d_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h1d ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Catechol-O-methyltransferase (COMT; E.C. 2.1.1.6) is a ubiquitous enzyme in nature that plays an important role in the metabolism of catechol neurotransmitters and xenobiotics. In particular, inactivation of drugs such as L-3,4-dihydroxyphenylalanine (L-DOPA) via O-methylation is of relevant pharmacological importance, because L-DOPA is currently the most effective drug used in the treatment of Parkinson's disease. This justified the interest in developing COMT inhibitors as potential adjuncts to L-DOPA therapy. The kinetics of inhibition by BIA 3-335 (1-[3,4-dihydroxy-5-nitrophenyl]-3-(N-3'-trifluormethylphenyl)-piperazine- 1-propanone dihydrochloride) were characterized using recombinant rat soluble COMT. BIA 3-335 was found to act as a potent, reversible, tight-binding inhibitor of COMT with a K(i) of 6.0 +/- 1.6 nM and displaying a competitive inhibition toward the substrate binding site and uncompetitive inhibition toward the S-adenosyl-L-methionine (SAM) binding site. The 2.0-A resolution crystal structure of COMT in complex with its cosubstrate SAM and a novel inhibitor BIA 3-335 shows the atomic interactions between the important residues at the active site and the inhibitor. This is the first report of a three-dimensional structure determination of COMT complexed with a potent, reversible, and tight-binding inhibitor that is expected to have therapeutic applications.
-===CATECHOL O-METHYLTRANSFERASE===
+Kinetics and crystal structure of catechol-o-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application.,Bonifacio MJ, Archer M, Rodrigues ML, Matias PM, Learmonth DA, Carrondo MA, Soares-Da-Silva P Mol Pharmacol. 2002 Oct;62(4):795-805. PMID:12237326<ref>PMID:12237326</ref>
-{{ABSTRACT_PUBMED_12237326}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1h1d" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[1h1d]] 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=1H1D OCA].
+*[[Catechol O-methyltransferase 3D structures|Catechol O-methyltransferase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:012237326</ref><references group="xtra"/>
+__TOC__
-[[Category: Catechol O-methyltransferase]]
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Archer, M.]]
+[[Category: Archer M]]
-[[Category: Bonifacio, M J.]]
+[[Category: Bonifacio MJ]]
-[[Category: Carrondo, M A.]]
+[[Category: Carrondo MA]]
-[[Category: Learmonth, D A.]]
+[[Category: Learmonth DA]]
-[[Category: Matias, P M.]]
+[[Category: Matias PM]]
-[[Category: Rodrigues, M L.]]
+[[Category: Rodrigues ML]]
-[[Category: Soares-Da-Silva, P.]]
+[[Category: Soares-da-Silva P]]
-[[Category: Methyltransferase]]
-[[Category: Neurotransmitter degradation]]
-[[Category: Transferase]]