Proteopedia - User contributions [en]

Daniel Eddelman Sandbox 2

2010-05-14T16:41:40Z

Daniel Eddelman: Daniel Eddelman Sandbox 2 moved to Citrate Synthase: Public recognition, required for class

#REDIRECT [[Citrate Synthase]]

Citrate Synthase

2010-05-14T16:41:40Z

Daniel Eddelman: Daniel Eddelman Sandbox 2 moved to Citrate Synthase: Public recognition, required for class

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is
-31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T08:14:26Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-22T08:11:16Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is
-31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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/1'>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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T08:02:45Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is
-31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]])<ref>PMID:7308213</ref>. This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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, citrate (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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:59:36Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is
-31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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, citrate (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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:59:09Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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, citrate (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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:57:56Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. Although it is a mitochondrial enzyme (in fact, it is often used as a quantitative enzyme marker for intact mitochondria), it is encoded by nuclear DNA, not mitochondrial <ref>"Citrate Synthase -." Wikipedia, the Free Encyclopedia. Web. 22 Mar. 2010. <http://en.wikipedia.org/wiki/Citrate_synthase></ref>. The standard free energy change (ΔG°’) for the citrate synthase reaction is -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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, citrate (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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:52:06Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. The standard free energy change (ΔG°’) for the citrate synthase reaction is -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

'''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, citrate (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>

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:43:58Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. The standard free energy change (ΔG°’) for the citrate synthase reaction is -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>. This negative free energy value means that citrate synthase is likely to function far from equilibrium under physiological conditions, and is thus a rate-determining enzyme in the citric acid cycle.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

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

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:37:17Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate. The standard free energy change (ΔG°’) for the citrate synthase reaction is -31.5kJ/mol <ref name="voet">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

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

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:34:09Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<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'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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">Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008.</ref>.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

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

<scene name='Daniel_Eddelman_Sandbox_2/Closed_default/1' target='closed' >Closed Default</scene>
<references/>

Citrate Synthase

2010-03-22T07:30:47Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:50:04Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:49:43Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:42:24Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:39:55Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:39:17Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<applet load='1cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Open Form' name='open'/>
Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

<applet load='2cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Closed Form' name='closed'/>

Citrate Synthase

2010-03-21T17:38:41Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<applet load='1cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Open Form' name='open'/>

<applet load='2cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Closed Form' name='closed'/>Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-03-21T17:37:52Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
<applet load='1cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Open Form' name='open'/>
<applet load='2cts' size='300' color='white' frame='true' align='right' caption='Citrate Synthase Closed Form' name='closed'/>Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-03-21T17:35:44Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

<applet load='2cts' size='250' color='white' frame='true' align='center' caption='Citrate Synthase Closed Form' name='closed'/>

Citrate Synthase

2010-03-21T17:34:54Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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' target='closed' >closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='0' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

<applet load='2cts' size='250' color='white' frame='true' align='center' caption='Citrate Synthase Closed Form' name='closed'/>

Citrate Synthase

2010-03-21T17:31:28Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

Citrate Synthase

2010-03-21T17:29:16Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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'target='closed'>closed conformation</scene> (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

<applet load='2cts' size='350' color='white' frame='true' align='right' name='closed' caption='Citrate Synthase Closed Form'/>

Citrate Synthase

2010-03-21T17:25:00Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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 closed conformation (PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

<applet load='2cts' size='350' color='white' frame='true' align='right' name='closed' caption='Citrate Synthase Closed Form'/>

Citrate Synthase

2010-03-21T17:09:48Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}{{STRUCTURE_2cts | PDB=2cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase is a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'target='0'>monomer</scene>. Biologically, however, it exists as a
<scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/2'target='0'>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 closed conformation (bottom image, PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-03-21T17:03:25Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}{{STRUCTURE_2cts | PDB=2cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase is a single amino acid chain <scene name='Daniel_Eddelman_Sandbox_2/Cts_open_monomer/1'Target='0'>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 closed conformation (bottom image, PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-03-21T16:59:22Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}{{STRUCTURE_2cts | PDB=2cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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 closed conformation (bottom image, PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-03-21T16:53:07Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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 closed conformation (bottom image, PDB: [[2cts]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T04:18:29Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1'>His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T04:15:33Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1'>Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1'>His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T04:06:59Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T04:05:14Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/2'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T04:00:44Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/1'>active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:46:36Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:43:41Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''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_homodimer/1'>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]]). This 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.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:34:28Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a <scene name='Daniel_Eddelman_Sandbox_2/Cts_homodimer/1'>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]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

File:2cts.mmol

2010-02-28T03:29:56Z

Daniel Eddelman:

Citrate Synthase

2010-02-28T03:27:40Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a <scene name='Daniel_Eddelman_Sandbox_2/Cts_homodimer/1'>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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:18:31Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a <scene name='Daniel_Eddelman_Sandbox_2/Cts_homodimer/1'>homodimer</scene>. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

File:1cts.mmol

2010-02-28T03:15:15Z

Daniel Eddelman: uploaded a new version of "Image:1cts.mmol"

homodimer of citrate synthase 1cts

Citrate Synthase

2010-02-28T03:04:35Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}{{STRUCTURE_2cts | PDB=2cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a
<scene name='Daniel_Eddelman_Sandbox_2/Binding_cleft/2'>cleft containing the substrate (oxaloacetate) binding site</scene> (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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:03:38Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a
<scene name='Daniel_Eddelman_Sandbox_2/Binding_cleft/2'>cleft containing the substrate (oxaloacetate) binding site</scene> (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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T03:00:51Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a
<scene name='Daniel_Eddelman_Sandbox_2/Binding_cleft/2'>cleft</scene> 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T02:53:28Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. In its free enzyme state, citrate synthase exists in “open” form, with its two domains forming a
<scene name='Daniel_Eddelman_Sandbox_2/Binding_cleft/1'>cleft</scene> 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T01:06:44Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T01:06:13Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T01:05:25Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation (PDB: [[2cts]]) <ref>PMID:7120407</ref>. This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T01:04:10Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation (PDB: [[2cts]]). This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>

Citrate Synthase

2010-02-28T01:03:15Z

Daniel Eddelman: /* The Structure and Mechanism of Citrate Synthase */

==The Structure and Mechanism of Citrate Synthase==
{{STRUCTURE_1cts | PDB=1cts | SCENE= }}Citrate synthase is an enzyme active in the mitochondria, where it is responsible for catalyzing the first reaction of the citric acid cycle (Krebs Cycle): the condensation of acetyl-CoA and oxaloacetate to form citrate.

'''Structure:''' Citrate synthase exists as a homodimer. Each identical subunit is comprised almost entirely of α helices (making it an all α protein) and consists of a large and a small domain. 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 “closed” conformation. This conformational change not only prevents solvent from reaching the bound oxaloacetate, but also generates the acetyl-CoA binding site. This presence of “open” and “closed” forms results in citrate synthase having Ordered Sequential kinetic behavior.

'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, ionizable side chains of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, Asp 375 (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. His 274 stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and His 320 donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA.

<references/>