5U6X

COX-1:P6 COMPLEX STRUCTURE

Summary for 5U6X

• Entry DOI: 10.2210/pdb5u6x/pdb
• Related: 3N8Z
• Descriptor: Prostaglandin G/H synthase 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cox-1, cyclooxygenase, peroxidase, prostaglandin, heme, p6, oxidoreductase
• Biological source: Ovis aries (Sheep)
• Total number of polymer chains: 2
• Total formula weight: 144027.05

Authors

Cingolani, G.,Panella, A.,Perrone, M.G.,Vitale, P.,Smith, W.L.,Scilimati, A. (deposition date: 2016-12-09, release date: 2017-08-09, Last modification date: 2024-11-06)

Primary citation

Cingolani, G.,Panella, A.,Perrone, M.G.,Vitale, P.,Di Mauro, G.,Fortuna, C.G.,Armen, R.S.,Ferorelli, S.,Smith, W.L.,Scilimati, A.
Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6).
Eur J Med Chem, 138:661-668, 2017

PubMed Abstract: The 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.

PubMed: 28710965
DOI: 10.1016/j.ejmech.2017.06.045

Experimental method

X-RAY DIFFRACTION (2.93 Å)