3TYM
Structure of neuronal nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(2-((2-methoxybenzyl)amino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine
Summary for 3TYM
| Entry DOI | 10.2210/pdb3tym/pdb |
| Related | 3TYL 3TYN 3TYO |
| Descriptor | Nitric oxide synthase, brain, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total) |
| Functional Keywords | nitric oxide synthase, inhibitor binding, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/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 | 100265.00 |
| Authors | Li, H.,Poulos, T.L. (deposition date: 2011-09-26, release date: 2012-03-14, Last modification date: 2023-09-13) |
| Primary citation | Labby, K.J.,Xue, F.,Kraus, J.M.,Ji, H.,Mataka, J.,Li, H.,Martasek, P.,Roman, L.J.,Poulos, T.L.,Silverman, R.B. Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase. Bioorg.Med.Chem., 20:2435-2443, 2012 Cited by PubMed Abstract: Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. PubMed: 22370337DOI: 10.1016/j.bmc.2012.01.037 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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