4JSJ

Structure of rat neuronal nitric oxide synthase heme domain in complex with 6-(((5-(((3-fluorophenethyl)amino)methyl)pyridin-3-yl)oxy)methyl)-4-methylpyridin-2-amine

Summary for 4JSJ

• Entry DOI: 10.2210/pdb4jsj/pdb
• Related: 4JSE 4JSF 4JSG 4JSH 4JSI 4JSK 4JSL 4JSM
• Descriptor: Nitric oxide synthase, brain, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total)
• Functional Keywords: nitric oxide synthase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Rattus norvegicus (rat)
• Cellular location: Cell membrane, sarcolemma ; Peripheral membrane protein : P29476
• Total number of polymer chains: 2
• Total formula weight: 100256.88

Authors

Li, H.,Poulos, T.L. (deposition date: 2013-03-22, release date: 2013-08-07, Last modification date: 2023-09-20)

Primary citation

Jing, Q.,Li, H.,Fang, J.,Roman, L.J.,Martasek, P.,Poulos, T.L.,Silverman, R.B.
In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.
Bioorg.Med.Chem., 21:5323-5331, 2013

PubMed Abstract: In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important to develop inhibitors selective for nNOS that do not interfere with other NOS isoforms, especially endothelial NOS (eNOS), which is critical for proper functioning of the cardiovascular system. While we have been successful in developing potent and isoform-selective inhibitors, such as lead compounds 1 and 2, the ease of synthesis and bioavailability have been problematic. Here we describe a new series of compounds including crystal structures of NOS-inhibitor complexes that integrate the advantages of easy synthesis and good biological properties compared to the lead compounds. These results provide the basis for additional structure-activity relationship (SAR) studies to guide further improvement of isozyme selective inhibitors.

PubMed: 23867386
DOI: 10.1016/j.bmc.2013.06.014

Experimental method

X-RAY DIFFRACTION (1.92 Å)