Sandbox 156: Difference between revisions

Line 24:

[[Image:512px-Acetyl-CoA-2D.svg.png|thumb|291x1000 px|right|Structure of Acetyl-CoA]]

The general structure of CAT III is dominated by a six stranded antiparallel <scene name='Sandbox_156/Scene_4/4'>β-sheet</scene> and 5 <scene name='Sandbox_156/Scene_4/3'>α-helices</scene> stacked against the ends and face of the protein, forming a structure known as an "open-faced sandwhich"<ref name="Leslie"/>. An extended β-strand forms an extension of the six stranded sheet to a seven stranded sheet that spans the interface of the subunit. Three identical monomers associate to form the trimeric protein with two <scene name='Sandbox_156/Scene_7/1'>cobalt</scene> ions acting as [http://en.wikipedia.org/wiki/Cofactor_%28biochemistry%29 cofactors].

The general structure of CAT III is dominated by a six stranded antiparallel <scene name='Sandbox_156/Scene_4/4'>β-sheet</scene> and 5 <scene name='Sandbox_156/Scene_4/3'>α-helices</scene> stacked against the ends and face of the protein, forming a structure known as an "open-faced sandwhich"<ref name="Leslie"/>. An extended β-strand forms an extension of the six stranded sheet to a seven stranded sheet that spans the interface of the subunit<ref name="Leslie"/>. Three identical monomers associate to form the trimeric protein with two <scene name='Sandbox_156/Scene_7/1'>cobalt</scene> ions acting as [http://en.wikipedia.org/wiki/Cofactor_%28biochemistry%29 cofactors]<ref>PMID: 2271709</ref>.

===The Chloramphenicol Binding Site===

The association of the monomeric subunits produces a well-defined pocket at the subunit interface, allowing for the binding of the chloramphenicol substrate. The <scene name='Sandbox_156/Scene_3/1'>chloramphenicol binding site</scene> of CAT III is lined with hydrophobic residues, allowing van der Waals interactions and 2 [http://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonds] to form betwen the eznyme and the substrate. A third hydrogen bond is mediated through a <scene name='Sandbox_156/Scene_4/2'>bridging water molecule</scene> and allows interaction between the the 1-hydroxyl of chloramphenicol and the hydroxyl of Tyr-174<ref name="Murray"/>.

The association of the monomeric subunits produces a well-defined pocket at the subunit interface, allowing for the binding of the chloramphenicol substrate<ref>PMID:2109633</ref>. The <scene name='Sandbox_156/Scene_3/1'>chloramphenicol binding site</scene> of CAT III is lined with hydrophobic residues, allowing van der Waals interactions and 2 [http://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonds] to form betwen the eznyme and the substrate<ref name="Leslie"/>. A third hydrogen bond is mediated through a <scene name='Sandbox_156/Scene_4/2'>bridging water molecule</scene> and allows interaction between the the 1-hydroxyl of chloramphenicol and the hydroxyl of Tyr-174<ref name="Murray"/>.

===The Acetyl-CoA Binding Site===

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<ref name="Leslie"/>. 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<ref name="Day"/>. The amino acids lining the tunnel are also primarily hydrophobic producing close contact between the substrate and aromatic residues. This tunneling allows the formation of van der Waals interactions between the [http://en.wikipedia.org/wiki/Adenine 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.

<scene name='Sandbox_156/Scene9/2'>pantetheine arm</scene> from the opposite side of the trimer<ref name="Day"/>. The amino acids lining the tunnel are also primarily hydrophobic producing close contact between the substrate and aromatic residues<ref>PMID:7906544</ref>. This tunneling allows the formation of van der Waals interactions between the [http://en.wikipedia.org/wiki/Adenine 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<ref name="Leslie"/>.

===The Active Site===

The active site catalyzes sequential acetylations of the chloramphenicol molecule. This is initiated by the deprotonation of the 3-hydroxyl of chloramphenicol by <scene name='Sandbox_156/Scene_two/1'>His-195</scene><ref name="Murray"/>. Numerous hydrogen bonds are present and, importantly, van der Waals interactions between the [http://en.wikipedia.org/wiki/Benzene benzene ring] of the <scene name='Sandbox_156/Scene_4/1'>Tyr-25</scene> residue and the [http://en.wikipedia.org/wiki/Imidazole imidazole ring]. This van der Waals contact may help stabilize side-chain orientations, promoting specificity in the reaction. The acetyl group is already properly positioned after tunneling, and reacts readily without any major structural changes<ref name="Leslie"/>.

The active site catalyzes sequential acetylations of the chloramphenicol molecule. This is initiated by the deprotonation of the 3-hydroxyl of chloramphenicol by <scene name='Sandbox_156/Scene_two/1'>His-195</scene><ref name="Murray"/>. Numerous hydrogen bonds are present and, importantly, van der Waals interactions between the [http://en.wikipedia.org/wiki/Benzene benzene ring] of the <scene name='Sandbox_156/Scene_4/1'>Tyr-25</scene> residue and the [http://en.wikipedia.org/wiki/Imidazole imidazole ring]<ref name="Day"/>. This van der Waals contact may help stabilize side-chain orientations, promoting specificity in the reaction. The acetyl group is already properly positioned after tunneling, and reacts readily without any major structural changes<ref name="Leslie"/>.

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@@ Line 24: / Line 24: @@
 <applet load='4CLA' size='300' frame='true' align='right' caption='' />
 [[Image:512px-Acetyl-CoA-2D.svg.png|thumb|291x1000 px|right|Structure of Acetyl-CoA]]
-The general structure of CAT III is dominated by a six stranded antiparallel <scene name='Sandbox_156/Scene_4/4'>β-sheet</scene> and 5 <scene name='Sandbox_156/Scene_4/3'>α-helices</scene> stacked against the ends and face of the protein, forming a structure known as an "open-faced sandwhich"<ref name="Leslie"/>. An extended β-strand forms an extension of the six stranded sheet to a seven stranded sheet that spans the interface of the subunit.  Three identical monomers associate to form the trimeric protein with two <scene name='Sandbox_156/Scene_7/1'>cobalt</scene> ions acting as [http://en.wikipedia.org/wiki/Cofactor_%28biochemistry%29 cofactors].
+The general structure of CAT III is dominated by a six stranded antiparallel <scene name='Sandbox_156/Scene_4/4'>β-sheet</scene> and 5 <scene name='Sandbox_156/Scene_4/3'>α-helices</scene> stacked against the ends and face of the protein, forming a structure known as an "open-faced sandwhich"<ref name="Leslie"/>. An extended β-strand forms an extension of the six stranded sheet to a seven stranded sheet that spans the interface of the subunit<ref name="Leslie"/>.  Three identical monomers associate to form the trimeric protein with two <scene name='Sandbox_156/Scene_7/1'>cobalt</scene> ions acting as [http://en.wikipedia.org/wiki/Cofactor_%28biochemistry%29 cofactors]<ref>PMID: 2271709</ref>.
 ===The Chloramphenicol Binding Site===
-The association of the monomeric subunits produces a well-defined pocket at the subunit interface, allowing for the binding of the chloramphenicol substrate. The <scene name='Sandbox_156/Scene_3/1'>chloramphenicol binding site</scene> of CAT III is lined with hydrophobic residues, allowing van der Waals interactions and 2 [http://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonds] to form betwen the eznyme and the substrate. A third hydrogen bond is mediated through a <scene name='Sandbox_156/Scene_4/2'>bridging water molecule</scene> and allows interaction between the the 1-hydroxyl of chloramphenicol and the hydroxyl of Tyr-174<ref name="Murray"/>.
+The association of the monomeric subunits produces a well-defined pocket at the subunit interface, allowing for the binding of the chloramphenicol substrate<ref>PMID:2109633</ref>. The <scene name='Sandbox_156/Scene_3/1'>chloramphenicol binding site</scene> of CAT III is lined with hydrophobic residues, allowing van der Waals interactions and 2 [http://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonds] to form betwen the eznyme and the substrate<ref name="Leslie"/>. A third hydrogen bond is mediated through a <scene name='Sandbox_156/Scene_4/2'>bridging water molecule</scene> and allows interaction between the the 1-hydroxyl of chloramphenicol and the hydroxyl of Tyr-174<ref name="Murray"/>.
 ===The Acetyl-CoA Binding Site===
-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<ref name="Leslie"/>. 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<ref name="Day"/>. The amino acids lining the tunnel are also primarily hydrophobic producing close contact between the substrate and aromatic residues. This tunneling allows the formation of van der Waals interactions between the [http://en.wikipedia.org/wiki/Adenine 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.
+<scene name='Sandbox_156/Scene9/2'>pantetheine arm</scene> from the opposite side of the trimer<ref name="Day"/>. The amino acids lining the tunnel are also primarily hydrophobic producing close contact between the substrate and aromatic residues<ref>PMID:7906544</ref>. This tunneling allows the formation of van der Waals interactions between the [http://en.wikipedia.org/wiki/Adenine 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<ref name="Leslie"/>.
 ===The Active Site===
-The active site catalyzes sequential acetylations of the chloramphenicol molecule. This is initiated by the deprotonation of the 3-hydroxyl of chloramphenicol by <scene name='Sandbox_156/Scene_two/1'>His-195</scene><ref name="Murray"/>. Numerous hydrogen bonds are present and, importantly, van der Waals interactions between the [http://en.wikipedia.org/wiki/Benzene benzene ring] of the <scene name='Sandbox_156/Scene_4/1'>Tyr-25</scene> residue and the [http://en.wikipedia.org/wiki/Imidazole imidazole ring]. This van der Waals contact may help stabilize side-chain orientations, promoting specificity in the reaction. The acetyl group is already properly positioned after tunneling, and reacts readily without any major structural changes<ref name="Leslie"/>.
+The active site catalyzes sequential acetylations of the chloramphenicol molecule. This is initiated by the deprotonation of the 3-hydroxyl of chloramphenicol by <scene name='Sandbox_156/Scene_two/1'>His-195</scene><ref name="Murray"/>. Numerous hydrogen bonds are present and, importantly, van der Waals interactions between the [http://en.wikipedia.org/wiki/Benzene benzene ring] of the <scene name='Sandbox_156/Scene_4/1'>Tyr-25</scene> residue and the [http://en.wikipedia.org/wiki/Imidazole imidazole ring]<ref name="Day"/>. This van der Waals contact may help stabilize side-chain orientations, promoting specificity in the reaction. The acetyl group is already properly positioned after tunneling, and reacts readily without any major structural changes<ref name="Leslie"/>.