4upn

Structure of rat neuronal nitric oxide synthase heme domain in complex with N,N-{[(2S)-3-aminopropane-1,2-diyl]bis(oxymethanediylbenzene-3,1-diyl)}dithiophene-2-carboximidamide

spinqualitylabelsall models 4upn, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4upn 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 2.09Å Ligands: 7LN, ACT, H4B, HEM, 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 To develop potent and selective nNOS inhibitors, a new series of double-headed molecules with chiral linkers that derive from natural amino acid derivatives have been designed and synthesized. The new structures integrate a thiophenecarboximidamide head with two types of chiral linkers, presenting easy synthesis and good inhibitory properties. Inhibitor (S)-9b exhibits a potency of 14.7nM against nNOS and is 1134 and 322-fold more selective for nNOS over eNOS and iNOS, respectively. Crystal structures show that the additional binding between the aminomethyl moiety of 9b and propionate A on the heme and tetrahydrobiopterin (H4B) in nNOS, but not eNOS, contributes to its high selectivity. This work demonstrates the advantage of integrating known structures into structure optimization, and it should be possible to more readily develop compounds that incorporate bioavailability with these advanced features. Moreover, this integrative strategy is a general approach in new drug discovery. Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase.,Jing Q, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB Bioorg Med Chem Lett. 2014 Aug 12. pii: S0960-894X(14)00814-2. doi:, 10.1016/j.bmcl.2014.07.079. PMID:25149509 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nitric Oxide Synthase 3D structures

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