Citrate Synthase: Difference between revisions

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'''Structure:''' Citrate synthase is a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>. Biologically, however, it exists as a

<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein). In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>. When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. ~~This~~ conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the states</scene>~~; the~~ conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.

<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene>. Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein). In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>. When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. The conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the

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'''Regulation:''' Perhaps the most crucial regulators of the citrate synthase reaction are its substrates, acetyl-CoA and oxaloacetate. Both are present in the mitochondria at concentrations below saturation of citrate synthase. The metabolic flux is controlled by substrate availability, so controlling the levels of acetyl-CoA and oxaloacetate in the mitochondria controls the rate of reaction. Furthermore, citrate synthase is inhibited by NADH, <scene name='Daniel_Eddelman_Sandbox_2/Citrate/2'>citrate</scene> (which competes with oxaloacetate), and succinyl-CoA (an example of competitive feedback inhibition) <ref>PMID:3013232</ref>.

<scene name='Daniel_Eddelman_Sandbox_2/Open_default/1' target='open' >Open Default</scene>

Citrate Synthase: Difference between revisions

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@@ Line 5: / Line 5: @@
 '''Structure:''' Citrate synthase is a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'>monomer</scene>.  Biologically, however, it exists as a
-<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene>.  Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein).  In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>.  When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>.   This conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the states</scene>; the conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site.  This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.
+<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'>homodimer</scene>.  Each identical subunit consists of a large and a small domain, and is comprised almost entirely of α helices (making it an all α protein).  In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a cleft containing the substrate (oxaloacetate) binding site (PDB: [[1cts]]) <ref>PMID:7120407</ref>.  When oxaloacetate binds, the smaller domain undergoes an 18° rotation, sealing the oxaloacetate binding site and resulting in the <scene name='Daniel_Eddelman_Sandbox_2/Closed_homodimer/1'>closed conformation of the homodimer</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>.   The conformational change is best illustrated via <scene name='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/1ctsto2ctsmorph/5'>a morph between the "open" and "closed" states</scene>. The conformational change not only prevents solvent from reaching the bound substrate, but also generates the acetyl-CoA binding site.  This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior <ref name="voet" />.
 '''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington.  In this mechanism, three ionizable side chains in the
@@ Line 13: / Line 13: @@
 '''Regulation:''' Perhaps the most crucial regulators of the citrate synthase reaction are its substrates, acetyl-CoA and oxaloacetate.  Both are present in the mitochondria at concentrations below saturation of citrate synthase.  The metabolic flux is controlled by substrate availability, so controlling the levels of acetyl-CoA and oxaloacetate in the mitochondria controls the rate of reaction.  Furthermore, citrate synthase is inhibited by NADH, <scene name='Daniel_Eddelman_Sandbox_2/Citrate/2'>citrate</scene> (which competes with oxaloacetate), and succinyl-CoA (an example of competitive feedback inhibition) <ref>PMID:3013232</ref>.
-<applet load='2cts' size='300' color='white' frame='true' align='right'  caption='Citrate Synthase Closed Form' name='closed'/> <applet load='1cts' size='300' color='white' frame='true' align='right'  caption='Citrate Synthase Open Form' name='open'/>
+<applet load='2cts' size='200' color='white' frame='true' align='right'  caption='Citrate Synthase Closed Form of (Monomer)' name='closed'/> <applet load='1cts' size='200' color='white' frame='true' align='right'  caption='Citrate Synthase Open Form (Monomer)' name='open'/>
 <scene name='Daniel_Eddelman_Sandbox_2/Open_default/1' target='open' >Open Default</scene>