1h1d

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|PDB= 1h1d |SIZE=350|CAPTION= <scene name='initialview01'>1h1d</scene>, resolution 2.0&Aring;
|PDB= 1h1d |SIZE=350|CAPTION= <scene name='initialview01'>1h1d</scene>, resolution 2.0&Aring;
|SITE= <scene name='pdbsite=MG1:Bia+Binding+Site+For+Chain+A'>MG1</scene>
|SITE= <scene name='pdbsite=MG1:Bia+Binding+Site+For+Chain+A'>MG1</scene>
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|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>
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|LIGAND= <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>
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|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]
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|ACTIVITY= <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>
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h1d OCA], [http://www.ebi.ac.uk/pdbsum/1h1d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h1d RCSB]</span>
}}
}}
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[[Category: Rodrigues, M L.]]
[[Category: Rodrigues, M L.]]
[[Category: Soares-Da-Silva, P.]]
[[Category: Soares-Da-Silva, P.]]
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[[Category: BIA]]
 
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[[Category: MG]]
 
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[[Category: SAM]]
 
[[Category: methyltransferase]]
[[Category: methyltransferase]]
[[Category: neurotransmitter degradation]]
[[Category: neurotransmitter degradation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:30:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:55:39 2008''

Revision as of 17:55, 30 March 2008


PDB ID 1h1d

Drag the structure with the mouse to rotate
, resolution 2.0Å
Sites:
Ligands: , ,
Activity: Catechol O-methyltransferase, with EC number 2.1.1.6
Resources: FirstGlance, OCA, PDBsum, RCSB
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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