Abstract
Two isoforms of prostaglandin H synthase (PGHS) are known, with PGHS-1 believed to be a housekeeping enzyme and PGHS-2 assigned roles in cell proliferation and inflammation1. Both isoforms have two catalytic activities: oxygenation of arachidonate to form PGG2 (cyclooxygenase), and reduction of PGG2 to form PGH2 (peroxidase). The overall amino acid identity between the human PGHS isoforms is about 60%, with much higher conservation in residues required for catalysis2. Crystallographic results have shown PGHS-1 and PGHS-2 to have very similar folding patterns3,4,5.
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References
H.R. Herschman, Prostaglandin synthase 2, Biochim. Biophys. Acta 1299:125 (1996).
T. Hla and K. Neilson, Human cyclooxygenase-2 cDNA, Proc. Natl. Acad. Sci. U.S.A. 89:7384 (1992).
D. Picot, P.J. Loll, and R,M, Garavito, The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1, Nature 367:243 (1994).
C. Luong, A. Miller, J. Barnett, J. Chow, C. Ramesha, and M.F. Browner, Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2, Nature Struct. Biol. 3:927 (1996).
R.G. Kurumbail, A.M. Stevens, J.K. Gierse, J.J. McDonald, R.A. Stegeman, J.Y. Pak, D. Gildehaus, J.M. Miyashiro, T.D. Penning, K. Seibert, P.C. Isakson, and W.C. Stallings, Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents, Nature 384:644 (1996).
J.K. Gierse, J.J. McDonald, S.D. Hauser, S.H. Rangwala, C.M. Koboldt, and K. Seibert, A single amino acid difference between cyclooxygenase-1 (COX-1) and-2 (COX-2) reverses the selectivity of COX-2 specific inhibitors, J. Biol. Chem. 271:15810 (1996).
Q. Guo, L.-H. Wang, K.-H. Ruan, and R.J. Kulmacz, Role of Val509 in time-dependent inhibition of human prostaglandin H synthase-2 cyclooxygenase activity by isoform-selective agents, J. Biol. Chem. 271:19134 (1996).
E. Wong, C. Bayly, H.L. Waterman, D. Riendeau, and J.A. Mancini, Conversion of prostaglandin G/H synthase-1 into an enzyme sensitive to PGHS-2-selective inhibitors by a double His513 — Arg and Ile523 — Val mutation, J. Biol. Chem. 272:9280 (1997).
G. Xiao, W. Chen, and R.J. Kulmacz, Comparison of structural stabilities of prostaglandin H synthase-1 and-2, J. Biol. Chem., in press (1998).
V. Houtzager, M. Ouellet, J.P. Falgueyret, L.A. Passmore, C. Bayly, and M.D. Percival, Inhibitor-induced changes in the intrinsic fluorescence of human cyclooxygenase-2, Biochemistry 35:10974 (1996).
C.-L. Tsou, Conformational flexibility of enzyme active sites, Science 262:380 (1993).
K.E. Neet and D.E. Timm, Conformational stability of dimeric proteins: quantitative studies by equilibrium denaturation, Protein Sci. 3:2167 (1994).
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Xiao, G., Chen, W., Kulmacz, R.J. (1999). Comparison of Prostaglandin H Synthase-1 and -2 Structural Stabilities. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E.A. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. Advances in Experimental Medicine and Biology, vol 469. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4793-8_17
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DOI: https://doi.org/10.1007/978-1-4615-4793-8_17
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