6GY1
rat COMT in complex with inhibitor
Summary for 6GY1
| Entry DOI | 10.2210/pdb6gy1/pdb |
| Descriptor | Catechol O-methyltransferase, MAGNESIUM ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total) |
| Functional Keywords | magnesium ion binding, o-methyltransferase activity, neurotransmitter catabolic process, transferase |
| Biological source | Rattus norvegicus (Rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 25720.72 |
| Authors | Schulze, M.-S. (deposition date: 2018-06-27, release date: 2018-10-10, Last modification date: 2025-12-10) |
| Primary citation | Buchler, I.,Akuma, D.,Au, V.,Carr, G.,de Leon, P.,DePasquale, M.,Ernst, G.,Huang, Y.,Kimos, M.,Kolobova, A.,Poslusney, M.,Wei, H.,Swinnen, D.,Montel, F.,Moureau, F.,Jigorel, E.,Schulze, M.E.D.,Wood, M.,Barrow, J.C. Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase. J. Med. Chem., 61:9647-9665, 2018 Cited by PubMed Abstract: A series of 8-hydroxy quinolines were identified as potent inhibitors of catechol O-methyltransferase (COMT) with selectivity for the membrane-bound form of the enzyme. Small substituents at the 7-position of the quinoline were found to increase metabolic stability without sacrificing potency. Compounds with good pharmacokinetics and brain penetration were identified and demonstrated in vivo modulation of dopamine metabolites in the brain. An X-ray cocrystal structure of compound 21 in the S-COMT active site shows chelation of the active site magnesium similar to catechol-based inhibitors. These compounds should prove useful for treatment of many neurological and psychiatric conditions associated with compromised cortical dopamine signaling. PubMed: 30272964DOI: 10.1021/acs.jmedchem.8b01126 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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