5u6x
From Proteopedia
COX-1:P6 COMPLEX STRUCTURE
Structural highlights
FunctionPGH1_SHEEP May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells. Publication Abstract from PubMedThe diarylisoxazole molecular scaffold is found in several NSAIDs, especially those with high selectivity for COX-1. Here, we have determined the structural basis for COX-1 binding to two diarylisoxazoles: mofezolac, which is polar and ionizable, and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6) that has very low polarity. X-ray analysis of the crystal structures of COX-1 bound to mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole allowed the identification of specific binding determinants within the enzyme active site, relevant to generate structure/activity relationships for diarylisoxazole NSAIDs. Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6).,Cingolani G, Panella A, Perrone MG, Vitale P, Di Mauro G, Fortuna CG, Armen RS, Ferorelli S, Smith WL, Scilimati A Eur J Med Chem. 2017 Jun 24;138:661-668. doi: 10.1016/j.ejmech.2017.06.045. PMID:28710965[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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