1h1d
From Proteopedia
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| - | [[Image:1h1d.gif|left|200px]] | + | [[Image:1h1d.gif|left|200px]] |
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| - | ''' | + | {{Structure |
| + | |PDB= 1h1d |SIZE=350|CAPTION= <scene name='initialview01'>1h1d</scene>, resolution 2.0Å | ||
| + | |SITE= <scene name='pdbsite=MG1:Bia+Binding+Site+For+Chain+A'>MG1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene> and <scene name='pdbligand=BIA:1-(3,4,DIHYDROXY-5-NITROPHENYL)-3-{4-[3-(TRIFLUOROMETHYL) PHENYL] PIPERAZIN-1-YL}PROPAN-1-ONE'>BIA</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CATECHOL O-METHYLTRANSFERASE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1H1D is a [ | + | 1H1D is a [[Single protein]] structure of 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]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12237326 12237326] |
[[Category: Catechol O-methyltransferase]] | [[Category: Catechol O-methyltransferase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
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[[Category: neurotransmitter degradation]] | [[Category: neurotransmitter degradation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:30:53 2008'' |
Revision as of 09:30, 20 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , and | ||||||
| Activity: | Catechol O-methyltransferase, with EC number 2.1.1.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CATECHOL O-METHYLTRANSFERASE
Overview
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 Structure
1H1D is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
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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