4ctq | pdb_00004ctq

Structure of rat neuronal nitric oxide synthase heme domain in complex with (R)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amine

spinqualitylabelsall models 4ctq, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ctq is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: ACT, H4B, HEM, S5D, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NOS1_RAT Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Publication Abstract from PubMed Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3 - 8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors. Nitric Oxide Synthase Inhibitors that Interact with both a Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity.,Kang S, Tang W, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Apr 23. PMID:24758147 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nitric Oxide Synthase 3D structures

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