2ZVJ
Crystal structures of rat Catechol-O-Methyltransferase complexed with coumarine-based inhibitor
Summary for 2ZVJ
| Entry DOI | 10.2210/pdb2zvj/pdb |
| Related | 1H1D 1JR4 1VID 2CL5 |
| Descriptor | Catechol O-methyltransferase, MAGNESIUM ION, S-ADENOSYLMETHIONINE, ... (5 entities in total) |
| Functional Keywords | transferase, methyltransferase, neurotransmitter degradation, alternative initiation, catecholamine metabolism, cell membrane, cytoplasm, magnesium, membrane, metal-binding, phosphoprotein, s-adenosyl-l-methionine, signal-anchor, transmembrane |
| Biological source | Rattus norvegicus (Rat) |
| Cellular location | Isoform 2: Cytoplasm. Isoform 1: Cell membrane; Single-pass type II membrane protein; Extracellular side: P22734 |
| Total number of polymer chains | 1 |
| Total formula weight | 25593.51 |
| Authors | Tsuji, E. (deposition date: 2008-11-07, release date: 2009-01-06, Last modification date: 2023-11-01) |
| Primary citation | Tsuji, E.,Okazaki, K.,Takeda, K. Crystal structures of rat catechol-O-methyltransferase complexed with coumarine-based inhibitor Biochem.Biophys.Res.Commun., 378:494-497, 2009 Cited by PubMed Abstract: In 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. PubMed: 19056347DOI: 10.1016/j.bbrc.2008.11.085 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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