1h1d: Difference between revisions
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[[Image:1h1d.gif|left|200px]]<br /><applet load="1h1d" size=" | [[Image:1h1d.gif|left|200px]]<br /><applet load="1h1d" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1h1d, resolution 2.0Å" /> | caption="1h1d, resolution 2.0Å" /> | ||
'''CATECHOL O-METHYLTRANSFERASE'''<br /> | '''CATECHOL O-METHYLTRANSFERASE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1H1D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with MG, SAM and BIA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=MG1:Bia Binding Site For Chain A'>MG1</scene>. Full crystallographic information is available from [http:// | 1H1D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=SAM:'>SAM</scene> and <scene name='pdbligand=BIA:'>BIA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=MG1:Bia+Binding+Site+For+Chain+A'>MG1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H1D OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: neurotransmitter degradation]] | [[Category: neurotransmitter degradation]] | ||
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Revision as of 10:45, 3 February 2008
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CATECHOL O-METHYLTRANSFERASE
OverviewOverview
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.
About this StructureAbout this Structure
1H1D is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Active as Catechol O-methyltransferase, with EC number 2.1.1.6 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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