Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2
- 1 November 1996
- journal article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 3 (11) , 927-933
- https://doi.org/10.1038/nsb1196-927
Abstract
The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.Keywords
This publication has 32 references indexed in Scilit:
- Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases 1The FASEB Journal, 1995
- Different Intracellular Locations for Prostaglandin Endoperoxide H Synthase-1 and −2Journal of Biological Chemistry, 1995
- Regulation of prostaglandin endoperoxide synthase (cyclooxygenase) isozyme expressionProstaglandins, Leukotrienes & Essential Fatty Acids, 1995
- Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase.Proceedings of the National Academy of Sciences, 1994
- Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus systemBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1994
- Characterization of the Genomic Structure, Chromosomal Location and Promoter of Human Prostaglandin H Synthase-2 GeneBiochemical and Biophysical Research Communications, 1994
- The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1Nature, 1994
- Human cyclooxygenase-2 cDNA.Proceedings of the National Academy of Sciences, 1992
- Tyrosyl radicals and their role in hydroperoxide-dependent activation and inactivation of prostaglandin endoperoxide synthaseBiochemistry, 1992
- Chapter 10 The eicosanoids: cyclooxygenase, lipoxygenase, and epoxygenase pathwaysNew Comprehensive Biochemistry, 1991