4xue | pdb_00004xue

Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd27b

spinqualitylabelsall models 4xue, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xue is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 43J, MG, SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function COMT_HUMAN 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. Publication Abstract from PubMed 3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg(2+). The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT).,Harrison ST, Poslusney MS, Mulhearn JJ, Zhao Z, Kett NR, Schubert JW, Melamed JY, Allison TJ, Patel SB, Sanders JM, Sharma S, Smith RF, Hall DL, Robinson RG, Sachs NA, Hutson PH, Wolkenberg SE, Barrow JC ACS Med Chem Lett. 2015 Jan 26;6(3):318-23. doi: 10.1021/ml500502d. eCollection, 2015 Mar 12. PMID:25815153 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Catechol O-methyltransferase 3D structures

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