3D Structure of Prostaglandin H2 Synthase!

PGHS

Let's have some chimey chime fun!!!
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*reset the view*
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*the EGF-like domain*
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The EGF-like domain consists of two small two stranded beta pleated sheets. Maybe you are wondering: "Why isn't that portion of PGHS just hanging (as shown in the current view) straight down?" The EGF-like domain is
held to the main body by a disulfide bond.
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*the membrane binding motif*
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Highligted are the 4 hydrophbic alpha helicies that make up the membrane binding motif. This part of the enzyme is embedded in the outer leaflet of the cell membrane (PGHS is a monotopic membrane protein). Because detergents are needed to remove PGHS from the membrane, PGHS is considered an integral membrane protein.
view the hydrophobic regions click here>>
Three of the four helicies attach to the membrane while the fourth connects the membrane binding motif to the main body of PGHS.

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*the catalytic domain*

The portion of PGHS that remains pink is the large globular catalytic domain. This domain contains the peroxidase and cyclooxygenase active sites.

view the peroxidase active site click here>>

GREEN - inside of these green boundaries is the haem, the active site.

RED - these seven residues partly enclose the peroxidase active site, however the solvent has access to the haem.

YELLOW - this ten residue curve sticks out from the enzyme's surface forming two small binding sites for PGG2 and the reducing substrate.

In the peroxidase reaction, the haem is oxidized and the substrate - PGG2 or other long fatty chain acids - is reduced. The output is PGH2.

To see another view, click here>>
This view shows how the RED residues enclose the site, but not entirely.

The peroxidase site started with PGG2...Where did that come from?

let's move to the cyclooxygenase active site. click here>>

Imagine that the bottom right of the black screen is the outside of a cell. The hydrophobic portions of the membrane binding motif are in white and are embedded in the membrane. This serves as the entrance from the inside of the cell to the cyclooxygenase active site for hydrophobic fatty acids.

TEAL - The Serine that aspirin acetylates to decrease inflammation. This blocks access to the upper part of the channel where the active site is located.

RED ORANGE - The Tyrosine is the farthest end of the channel. This area is the cyclooxygenase active site.

In the cyclooxygenase reaction, arachidonic acid is converted to PGG2. You can see that this active site is very close to the peroxidase active site. Once PGG2 is produced in the cyclooxygenase site, it is passed to the peroxidase site and there converted into prostaglandin H2. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
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amreid@davidson.edu