Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2001 Jun;107(11):1335-7.
doi: 10.1172/JCI13037.

COX in a crystal ball: current status and future promise of prostaglandin research

G A FitzGerald  1 , P Loll
Affiliations
Review

COX in a crystal ball: current status and future promise of prostaglandin research

G A FitzGerald et al. J Clin Invest. 2001 Jun.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
The COX-1 and COX-2 backbones, overlaid. COX-1 is shown in yellow, and COX-2 in pink. Note how the two structures are almost perfectly superimposable. The amphipathic helices that form the site of monotopic membrane attachment are indicated. The peroxidase (POX) active site lies on the opposite side of the molecule from the entrance to the COX active site channel. The actual position of the COX active center is marked by the asterisk, found near the center of the molecule.
Figure 2
Figure 2
Isoform-selective inhibitor binding. The COX-1 and COX-2 active sites are shown superimposed (COX-1, yellow; COX-2, pink). Two inhibitors are seen: flurbiprofen (orange), a nonselective inhibitor, and SC-558 (blue), a COX-2–selective inhibitor. NSAIDs achieve COX inhibition by occupying the upper portion of the active site channel, preventing the fatty acid substrate from gaining access to the active site tyrosine seen at the upper right. Note how the COX-2–selective inhibitor projects leftward into a side pocket that is not exploited by the nonselective inhibitor.
Figure 3
Figure 3
A view of the “side pocket” found at the side of the COX-2 active site. The COX-2–selective inhibitor SC-558 is shown in blue, bound in the active site. Protein residues are shown as van der Waals spheres; valine 434 and valine 523 are shown in pink. In COX-1, both these residues are isoleucines; the additional bulk contributed by the two extra methyl groups is sufficient to close down this small alcove so that no side pocket is found in COX-1.
See this image and copyright information in PMC

References

    1. Gryglewski R, Vane JR. The release of prostaglandins and rabbit aorta contracting substance (RCS) from rabbit spleen and its antagonism by anti-inflammatory drugs. Br J Pharmacol. 1972;45:37–47. - PMC - PubMed
    1. Moncada S, Ferreira SH, Vane JR. Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature. 1973;246:217–219. - PubMed
    1. Oates JA. The 1982 Nobel prize in physiology or medicine. Science. 1982;218:765–768. - PubMed
    1. DeWitt DL, Smith WL. Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. Proc Natl Acad Sci USA. 1988;85:1412–1416. - PMC - PubMed
    1. Xie W, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA. 1991;88:2692–2696. - PMC - PubMed

MeSH terms