4imx

Structure of bovine endothelial nitric oxide synthase heme domain in complex with 3,5-bis(2-(6-amino-4-methylpyridin-2-yl)ethyl)benzonitrile

spinqualitylabelsall models 4imx, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4imx is a 2 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1EV, ACT, CAD, GOL, H4B, HEM, ZN Related: 4ims, 4imt, 4imu, 4imw Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of l-arginine to l-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. Here, we present a structure-guided, selective nNOS inhibitor design based on the crystal structure of lead compound 1 in nNOS. The best inhibitor, 7, exhibited low nanomolar inhibitory potency and good isoform selectivities (nNOS over eNOS and iNOS are 472-fold and 239-fold, respectively). Consistent with the good selectivity, 7 binds to nNOS and eNOS with different binding modes. The distinctly different binding modes of 7, driven by the critical residue Asp597 in nNOS, offers compelling insight to explain its isozyme selectivity, which should guide future drug design programs. Structure-guided design of selective inhibitors of neuronal nitric oxide synthase.,Huang H, Li H, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2013 Apr 11;56(7):3024-32. doi: 10.1021/jm4000984. Epub 2013 Mar 28. PMID:23451760 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA