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COX is a common target for anti-inflammatory drugs. The most significant difference between the isoenzymes, which allows for selective inhibition, is the substitution of isoleucine at position 523 in COX-1 with valine in COX-2. The smaller Val 523 residue in COX-2 allows access to a hydrophobic side-pocket in the enzyme (which Ile 523 ...
A splice variant of COX-1 termed COX-3 was identified in the central nervous system of dogs, but does not result in a functional protein in humans. Two smaller COX-1-derived proteins (the partial COX-1 proteins PCOX-1A and PCOX-1B) have also been discovered, but their precise roles are yet to be described. [10]
Cyclooxygenase-2 (COX-2), also known as prostaglandin-endoperoxide synthase 2 (HUGO PTGS2), is an enzyme that in humans is encoded by the PTGS2 gene. [5] In humans it is one of three cyclooxygenases. It is involved in the conversion of arachidonic acid to prostaglandin H 2, an important precursor of prostacyclin, which is expressed in inflammation.
COX-1 is responsible for the baseline levels of prostaglandins. COX-2 produces prostaglandins through stimulation. However, while COX-1 and COX-2 are both located in the blood vessels, stomach and the kidneys, prostaglandin levels are increased by COX-2 in scenarios of inflammation and growth.
Structure of COX-2 inactivated by Aspirin. In the active site of each of the two enzymes, Serine 516 has been acetylated. Also visible is the salicylic acid which has transferred the acetyl group, and the heme cofactor. There are at least two different cyclooxygenase isozymes: COX-1 (PTGS1) and COX-2 (PTGS2).
The two enzymes were renamed COX-1, referring to the original enzyme and COX-2. [5] Building on those results, scientists started focusing on selective COX-2 inhibitors . Enormous effort was spent on the development of NSAIDs between the 1960s and 1980 so there were numerous pharmacophores to test when COX-2 was discovered.
Heme B or haem B (also known as protoheme IX) is the most abundant heme. [1] Hemoglobin and myoglobin are examples of oxygen transport proteins that contain heme B. The peroxidase family of enzymes also contain heme B. The COX-1 and COX-2 enzymes (cyclooxygenase) of recent fame, also contain heme B at one of two active sites.
The conversion from arachidonic acid to prostaglandin H 2 is a two-step process. First, COX-1 catalyzes the addition of two free oxygens to form the 1,2-dioxane bridge and a peroxide functional group to form prostaglandin G 2 (PGG 2). [3] Second, COX-2 reduces the peroxide functional group to a secondary alcohol, forming prostaglandin H 2.