Rameia's Fun with Jolecule

Cyclooxygenase 

Rameia Ramsey 

 The protein I choose to examine and learn about is Cyclooxygenase. Cyclooxygenase, also known as COX, is an enzyme that is responsible for the creating of prostanoids, which are involved in the inflammatory responses. There are three main groups of prostanoids, which are the prostaglandins, prostacyclins, and thromboxanes. Prostaglandins are mediators of inflammatory and anaphylactic reactions, prostacyclins are seen in the resolution phase of inflammation, and thromboxanes are mediators of vasoconstriction, which is the narrowing of blood vessels from contractions from the muscular walls.

There are two forms of the Cyclooxygenase protein respectively named , COX-1 and COX-2. Both of these versions use arachidonic acid to produce prostaglandin but there are certain features that help make COX-1 unfavorable and COX-2 favorable. There are such things called COX-1 inhibitors, these are agents that hinder the action of the enzyme COX-1. The COX-1 enzyme is found in most cells and helps maintain the stomach’s. For example, inflammatory drugs such as aspirin or ibuprofen block the actions of COX-1 and COX-2. The COX-1 inhibitors are able to decrease inflammation but they can also decrease the protective mucus in one’s stomach, which in turn can cause a variety of health concerns such as an upset stomach or ulcers. This is how a COX-1 inhibitor can be seen as undesirable and unfavored. COX-2 inhibitors are agents that block the enzyme COX-2 which causes inflammation. The COX-2 enzyme converts arachidonic acid to prostaglandin which cause pain and inflammation, such as arthritis, in an individual's body. The COX-2 inhibitors relieves this pain. So drugs such as Bextra and Vioxx are examples of COX-2 inhibitors that help protect against the COX-2 enzyme. This is how COX-2 would be seen as more favorable to than COX-1.

Both COX-1 and COX-2 are tertiary structures because of the fact that the amino acids and the binding site and catalytic regions are almost exactly the same.  COX-1 and COX-2 are both homodimers. A dimer is a chemical compound that is made of two identical or similar monomers. A homodimers would be a dimer made of two identical monomers. They also both contain three high mannose oligosaccharides, a fourth oligosaccharide is found only in COX-2 which helps with its degradation. Each monomer of the dimer has three domains, which are the epidermal growth factor, membrane binding, and catalytic domain. On the other side of the membrane binding domain is the peroxidase active site which contains the heme. The active site of COX-2 is larger than the active site for COX-1. There are many differences between the two. COX-1 is produced under all types of physiological conditions, while COX-2 is produced only during specific conditions like inflammation. This would also explain why COX- 1 is found in the kidneys, stomach, and platelets and COX-2 is found in macrophages, leukocytes, and fibroblasts. They are also produced differently, COX-1 is made continuously while COX-2 is only produced when needed. COX-1 is useful to ones body and does not need the aid of inhibitors, but COX-2 plays a major role in inflammation and therefore inhibitors are needed for the COX-2 enzyme.

This is an aspirin molecule in the Cyclooxygenase protein.

This is the bonding site of the aspirin molecule.  This is what prevents the arachidonic acid which eventually gets converted into prostaglandin from binding.

This is the tunnel that leads to the active site.