1h1d

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[[Image:1h1d.gif|left|200px]]
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{{Seed}}
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[[Image:1h1d.png|left|200px]]
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{{STRUCTURE_1h1d| PDB=1h1d | SCENE= }}
{{STRUCTURE_1h1d| PDB=1h1d | SCENE= }}
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'''CATECHOL O-METHYLTRANSFERASE'''
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===CATECHOL O-METHYLTRANSFERASE===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_12237326}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12237326 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12237326}}
==About this Structure==
==About this Structure==
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[[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 Fri May 2 18:17:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:27:40 2008''

Revision as of 03:27, 1 July 2008

Image:1h1d.png

Template:STRUCTURE 1h1d

CATECHOL O-METHYLTRANSFERASE

Template:ABSTRACT PUBMED 12237326

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

Page seeded by OCA on Tue Jul 1 06:27:40 2008

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