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From Proteopedia
Crystal structures of rat Catechol-O-Methyltransferase complexed with coumarine-based inhibitor
Structural highlights
FunctionCOMT_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn human, catechol-O-methyltransferase (COMT: E.C. 2.1.1.6) is responsible for metabolism of catechol neurotransmitter and xenobiotics. The main clinical interest in COMT results from the possibility of using COMT inhibitors as adjuncts in the therapy of Parkinson's disease (PD) with l-DOPA. COMT is therefore a target for inhibitor development aiming at PD treatment and has been submitted to extensive structure-based drug design. Recently reported inhibitors have nitrocatechol structure that may inhibit oxidative phosphorylation and uncouple mitochondrial energy production. This work reports the first crystallographic study of Rat COMT complexed with non-nitrocatechol inhibitor. Analysis of the structural differences among the previously reported inhibitor complexes, coumarine-based inhibitor (4-phenyl-7, 8-dihydroxycoumarine: 4PCM) bound structure provides the explanation for inhibitor binding and can be used for future inhibitor design. Crystal structures of rat catechol-O-methyltransferase complexed with coumarine-based inhibitor.,Tsuji E, Okazaki K, Takeda K Biochem Biophys Res Commun. 2009 Jan 16;378(3):494-7. Epub 2008 Dec 3. PMID:19056347[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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