Sandbox 156: Difference between revisions
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Found in bacteria, the CAT III enzyme is responsible for conferring resistance of the antibiotic chloramphenicol to the cell. Chloramphenicol arrests protein synthesis by binding to the bacterial ribosomes and causing the inhibition of [http://en.wikipedia.org/wiki/Peptidyl_transferase peptidyl transferase] activity<ref>PMID: 1544895</ref>. However, when CAT III catalyzes the acetylation of chloramphenicol, the antibiotic can no longer bind to the ribosomes and is rendered inactive. The genes for the enzyme are commonly found on the plasmid of the bacteria and have been found in a numerous bacterial species<ref>PMID: 2268277</ref>. | Found in bacteria, the CAT III enzyme is responsible for conferring resistance of the antibiotic chloramphenicol to the cell. Chloramphenicol arrests protein synthesis by binding to the bacterial ribosomes and causing the inhibition of [http://en.wikipedia.org/wiki/Peptidyl_transferase peptidyl transferase] activity<ref>PMID: 1544895</ref>. However, when CAT III catalyzes the acetylation of chloramphenicol, the antibiotic can no longer bind to the ribosomes and is rendered inactive. The genes for the enzyme are commonly found on the plasmid of the bacteria and have been found in a numerous bacterial species<ref>PMID: 2268277</ref>. | ||
The multifunctional enzyme consists of three identical subunits with three active sites at the subunit interfaces. The side chains of one subunit allow van der Waals | The multifunctional enzyme consists of three identical subunits with three active sites at the subunit interfaces. The side chains of one subunit allow [http://en.wikipedia.org/wiki/Van_der_Waals_force van der Waals interactions] and two hydrogen bonds with chloramphenicol, causing binding of the substrate. The opposing subunit provides a histidine (His-195) residue essential for catalysis<ref>PMID: 8407936</ref>. Water molecules in the cavity provide a bridging hydrogen bond between the 1-hydroxyl of chloramphenicol and the hydroxyl of a threonine (Thr-174) residue. The active site of CAT III performs two acetylations of chloramphenicol and can accommodate the presence of the first intermediates quite well<ref>PMID:2015231</ref>. | ||
=== Reaction of CAT III === | === Reaction of CAT III === | ||
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The binding of chloramphenicol blocks acetyl-CoA from entering the active site from the <scene name='Sandbox_156/Scene9/1'>top of the enzyme</scene>, as illustrated. Instead, the second substrate tunnels to the active site through the | The binding of chloramphenicol blocks acetyl-CoA from entering the active site from the <scene name='Sandbox_156/Scene9/1'>top of the enzyme</scene>, as illustrated. Instead, the second substrate tunnels to the active site through the | ||
<scene name='Sandbox_156/Scene9/2'>pantetheine arm</scene> from the opposite side of the trimer. The amino acids lining the tunnel are also primarily lined with hydrophobic residues allowing for close contact between the substrate and aromatic residues<ref>PMID: 1544895</ref>. This tunneling allows the formation of | <scene name='Sandbox_156/Scene9/2'>pantetheine arm</scene> from the opposite side of the trimer. The amino acids lining the tunnel are also primarily lined with hydrophobic residues allowing for close contact between the substrate and aromatic residues<ref>PMID: 1544895</ref>. This tunneling allows the formation of van der Waals interactions between the adenine ring of acetyl-CoA with dimethyl groups of the pantetheine arm and hydrogen bonding of the ring with Tyr-56,Phe-96 and Phe-103, binding the substrate. | ||
===The Active Site=== | ===The Active Site=== | ||
