3RQJ
Structure of the neuronal nitric oxide synthase heme domain in complex with 6-(((3R,4R)-4-(2-((1S,2R)-2-(3-Fluorophenyl)cyclopropylamino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine
Summary for 3RQJ
| Entry DOI | 10.2210/pdb3rqj/pdb |
| Related | 3RQK 3RQL 3RQM 3RQN 3RQO 3RQP |
| Descriptor | Nitric oxide synthase, brain, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total) |
| Functional Keywords | oxidoreductase, enzyme-inhibitor complex, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor |
| Biological source | Rattus norvegicus (brown rat,rat,rats) |
| Cellular location | Cell membrane, sarcolemma ; Peripheral membrane protein : P29476 |
| Total number of polymer chains | 2 |
| Total formula weight | 100293.00 |
| Authors | Li, H.,Delker, S.L.,Poulos, T.L. (deposition date: 2011-04-28, release date: 2012-05-02, Last modification date: 2023-09-13) |
| Primary citation | Li, H.,Xue, F.,Kraus, J.M.,Ji, H.,Labby, K.J.,Mataka, J.,Delker, S.L.,Martasek, P.,Roman, L.J.,Poulos, T.L.,Silverman, R.B. Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase. Bioorg.Med.Chem., 21:1333-1343, 2013 Cited by PubMed Abstract: Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure-activity relationship (SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors. PubMed: 23352768DOI: 10.1016/j.bmc.2012.12.019 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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