Sara Fun with Jolecule Article

Sara Bearden

Cyclooxygenase

        After playing around in the program Jolecule I chose to learn more about the protein Cyclooxygenase.  This protein is know to be the site of pain-killing.  This protein is involved in the first step of creating postaglandins from a common fatty acid.  These postaglandins are what deliver and strengthen pain signals, induce inflammation, and control the constriction of muscle cells. There are different postaglandins that control different processes but, they are all created form the cyclooxygenase protein.  In order to create postaglandins the cyclooxygenase adds two oxygen molecules to arachidonic acid to start a set of reactions that will create a host of unusual molecules.  As we know the drug aspirin is used as a pain killer well, that drug blocks the binding of the arachidonic acid in the cyclooxygenase active site. That leads to a different product so new messages are delivered and we end up not feeling pain and don't launch an inflammation response.  There are two isomers of this protein and they are used for different purposes.  COX-1 is used for creating postaglandins in order to send basic housekeeping messages to the body in different cells.  COX-2 is used only in certain cells in order to signal pain and inflammation.

         The quaternary structure of this protein is a dimer of identical subunits so there are two active sites of cyclooxygenase and two peroxide active sites ( activate the heme groups that participate in the cyclooxygenase reaction). By having this structure the active sites are close by allowing the reaction to occur quicker and smoother. Each subunit has a knob that is covered with hydrophobic amino acids which allows anchorage to the membrane of the endoplasmic reticulum.  Therefore, the structure doesn't move and the acid that is used for the reaction can find the protein to do the reaction. The cyclooxygenase active site is reached by a tunnel in the protein which leads the arachidonic acid to the enzyme for processing and starting the reaction.  Aspirin can block this site so the reaction cannot occur and leading to different messages being delivered where we end up with feeling no pain. 

 This photo shows how the active site of cyclooxygenase is deep inside the protein.  The ribbon in front of it is the tunnel that would lead the arachodine acid to the active site to bind and start the set of reactions.  At that site is also where the aspirin would go and stop the binding from happening.

 The two active sites of the protein are shown in this photo.  The top one would be the the cyclooxygenase active site where the bottom would be the peroxide active site.  As shown in the photo the two sites are near each other and this is due to the structure of the protein.

 This screenshot shows some of the structures the atoms formed within the shape of cyclooxygenase.  These pentagon shapes are showing how they are non-polar because there are no water molecules around them.  Therefore, the bonds are equally sharing the electrons. Also making the whole protein non-polar which, means it's hydrophobic.

The last screenshot is an overview of the structure of the protein.  You can see the alpha helices intertwine with each other to form the the quaternary structure of a dimer.  There is are two identical subunits that are apart of the dimer which allows for double the active sites and with the alpha helices as a tertiary structure the active sites are in proximity of each other.