2bhj

murine iNO synthase with coumarin inhibitormurine iNO synthase with coumarin inhibitor

Structural highlights

2bhj is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NOS2_MOUSE Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.

Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase.,Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:15781384^[2]

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

References

↑ Kim SF, Huri DA, Snyder SH. Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science. 2005 Dec 23;310(5756):1966-70. PMID:16373578 doi:http://dx.doi.org/10.1126/science.1119407
↑ Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS. Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase. Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:15781384 doi:10.1016/j.bmc.2005.02.036

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OCA

[1] Kim SF, Huri DA, Snyder SH. Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science. 2005 Dec 23;310(5756):1966-70. PMID:16373578 doi:http://dx.doi.org/10.1126/science.1119407

[2] Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS. Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase. Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:15781384 doi:10.1016/j.bmc.2005.02.036

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