Sandbox Reserved 1471: Difference between revisions

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===Domains===

COX-1 is made up of 576 amino acids and COX-2 is made up of 581 amino acids.<ref name="Rouzer" /> The sequences match with 60% identical amino acids.<ref name="Rouzer" /> The structures of these isozymes are nearly superimposable with three domains each. The <scene name='80/800650/Membrane_bound_domain/1'>membrane binding domain</scene> made up of residues 73-116, goes through half of the lipid bilayer.<ref name="Picot" /> These residues are hydrophobic because they are in a hydrophobic environment with the fatty acid tails of the lipids surrounding this domain. Residues 117-587 make up the <scene name='80/800650/Catalytic_domain/2'>catalytic domain</scene>.<ref name="Picot" /> The catalytic domain has two catalytic active sites for each of the catalytic activities of cyclooxygenase and peroxidase. The third domain is similar to an <scene name='80/800650/Egf_domain/1'>epidermal growth factor (EGF) domain</scene>.<ref name="Picot" /> The function of the EGF domain is not fully understood, but it is speculated to help with structure stability and protein-protein interactions.<ref name="Picot" /> This domain is linked to the catalytic domain by disulfide bridges between Cys 37- Cys 159.<ref name="Picot" />

===Reaction===

Arachidonic acid can bind in the nonproductive conformation and the productive conformation.<ref name="Vecchio">PMID:20463020</ref> In the nonproductive conformation, the carboxyl of arachidonic acid is interacting with Tyrosine 385 and Serine 530.<ref name="Vecchio" /> The productive conformation has the carboxyl of arachidonic acid interacting with Arginine 120 and Tyrosine 355 which leaves Tyrosine 385 available to take the pro-S hydrogen from carbon 13.<ref name="Vecchio" /> In other words, the productive conformation yields a reaction and product while the nonproductive conformation does not. In figure 2 and 3, Tyrosine 385 is colored in cyan. These figures show how the residues is in the middle of the cyclooxygenase channel and can easily be inhibited by Rofecoxib blocking the cyclooxygenase active site. In these images, the membrane binding domain is colored in red and the catalytic domain is colored in blue. Figure 3 shows the peroxidase active site with the protoporphyrin IX containing cobalt. Other structure showed a heme group interacting with COX. There does not seem to be a preference over the protoporphyrin verses the heme group. Sticking with the PDB file of 5KIR, the proximal Histidine 388 and the distal Histidine 207 coordinate the protoporphyrin group colored in cyan.<ref name="Orlando" />

===Heteroatoms of the PDB file 5KIR<ref name="Orlando" />===

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 ===Domains===
 COX-1 is made up of 576 amino acids and COX-2 is made up of 581 amino acids.<ref name="Rouzer" /> The sequences match with 60% identical amino acids.<ref name="Rouzer" /> The structures of these isozymes are nearly superimposable with three domains each. The <scene name='80/800650/Membrane_bound_domain/1'>membrane binding domain</scene> made up of residues 73-116, goes through half of the lipid bilayer.<ref name="Picot" /> These residues are hydrophobic because they are in a hydrophobic environment with the fatty acid tails of the lipids surrounding this domain. Residues 117-587 make up the <scene name='80/800650/Catalytic_domain/2'>catalytic domain</scene>.<ref name="Picot" /> The catalytic domain has two catalytic active sites for each of the catalytic activities of cyclooxygenase and peroxidase. The third domain is similar to an <scene name='80/800650/Egf_domain/1'>epidermal growth factor (EGF) domain</scene>.<ref name="Picot" /> The function of the EGF domain is not fully understood, but it is speculated to help with structure stability and protein-protein interactions.<ref name="Picot" /> This domain is linked to the catalytic domain by disulfide bridges between Cys 37- Cys 159.<ref name="Picot" />
+===Reaction===
+Arachidonic acid can bind in the nonproductive conformation and the productive conformation.<ref name="Vecchio">PMID:20463020</ref> In the nonproductive conformation, the carboxyl of arachidonic acid is interacting with Tyrosine 385 and Serine 530.<ref name="Vecchio" /> The productive conformation has the carboxyl of arachidonic acid interacting with Arginine 120 and Tyrosine 355 which leaves Tyrosine 385 available to take the pro-S hydrogen from carbon 13.<ref name="Vecchio" /> In other words, the productive conformation yields a reaction and product while the nonproductive conformation does not. In figure 2 and 3, Tyrosine 385 is colored in cyan. These figures show how the residues is in the middle of the cyclooxygenase channel and can easily be inhibited by Rofecoxib blocking the cyclooxygenase active site. In these images, the membrane binding domain is colored in red and the catalytic domain is colored in blue. Figure 3 shows the peroxidase active site with the protoporphyrin IX containing cobalt. Other structure showed a heme group interacting with COX. There does not seem to be a preference over the protoporphyrin verses the heme group. Sticking with the PDB file of 5KIR, the proximal Histidine 388 and the distal Histidine 207 coordinate the protoporphyrin group colored in cyan.<ref name="Orlando" />
 ===Heteroatoms of the PDB file 5KIR<ref name="Orlando" />===