PGH2 Synthase

PDB file 1PGE

This file depicts PGH2 Synthase (Cyclooxygenase) co-crystallized with an iodinated NSAID  iodosuprofen (ISF, an analog of Ibuprofen). The structure was solved by P. J. Loll, D. Picot, & R. M. Garavito in 1995.

Suggested display options:

Color chain, to distinguish the 2 polypeptides of the dimer.
Select
hetero-ligand, display as ball & stick with color CPK.
Identify each of the following ligands:
heme (HEM, the prosthetic group)
iodosuprofen (ISF, note the I)
b-octylglucoside (BOG, a detergent used to solublize the enzyme)
N-acetyl glucosamine residues (NAG).

Before examining active site residues, you might want to make octylglucoside & NAG disappear. Select residues BOG and NAG, and select hide.

Now
visualize the position of each of the following relative to the heme and iodosuprofen:
tyr385, forms a transient radical during catalysis.
ser530, the residue that can be acetylated by aspirin.
arg120, which forms an ion pair with the carboxyl of ISF in the hydrophobic "channel" through which arachidonate normally approaches the heme.
70-117, the membrane-binding domain. Select these residues, display as cartoon and color structure so that you can view its secondary structure.

Now display the protein as spacefill.
Answer the following questions: (Try giving a different color to hydrophobic and polar residues, and experiment with slab mode.)
Is the tunnel leading from the membrane to the heme very spacious?
Is it largely lined with polar or hydrophobic groups? Is this what you would expect?
What is the significance of the location of hydrophobic residues in the membrane-binding domain?


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