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4jsi

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

Structural highlights

4jsi 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:	, , , ,
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

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.

In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures.,Jing Q, Li H, Fang J, Roman LJ, Martasek P, Poulos TL, Silverman RB Bioorg Med Chem. 2013 Jun 15. pii: S0968-0896(13)00545-2. doi:, 10.1016/j.bmc.2013.06.014. PMID:23867386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jing Q, Li H, Fang J, Roman LJ, Martasek P, Poulos TL, Silverman RB. In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures. Bioorg Med Chem. 2013 Jun 15. pii: S0968-0896(13)00545-2. doi:, 10.1016/j.bmc.2013.06.014. PMID:23867386 doi:10.1016/j.bmc.2013.06.014