Citrate Synthase: Difference between revisions
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<StructureSection load='1cts' size='450' side='right' scene='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/Camorph/5' caption=''> | <StructureSection load='1cts' size='450' side='right' scene='User:Wayne_Decatur/1cts_to_2cts_(citrate_synthase)_morph_methods/Camorph/5' caption=''> | ||
[[Image:2cts plus overall reaction.png| | [[Image:2cts plus overall reaction.png|200px|left|thumb| <span style="font-size:1.2em;">Citrate synthase 'closed' form ([[2cts]]) and the reaction</span>]] | ||
==The Structure and Mechanism of Citrate Synthase== | ==The Structure and Mechanism of Citrate Synthase== | ||
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{{Link Toggle FancyCartoonHighQualityView}} | {{Link Toggle FancyCartoonHighQualityView}} | ||
'''Mechanism:''' <scene name='Citrate_Synthase/5ctsactivesitedimer/2'>Three side chains in each of the two active sites</scene> of the dimer contribute directly to the chemistry of catalysis. Focusing on a single active site in the closed conformation, one can easily observe that <scene name='Citrate_Synthase/5ctsactivesiteresidues/10'>these three side chains and the two substrates are together</scene> in an arrangement favorable for reaction. (By contrast, <scene name='Citrate_Synthase/Activesite1ctsto2cts/12'>the active site residues are significantly farther apart</scene> in the open conformation; the difference in the distance is ~5Å along the axis that changes the most during the conformation shift.) {{Link Toggle AnimationOnPause}} | '''Mechanism:''' <scene name='Citrate_Synthase/5ctsactivesitedimer/2'>Three side chains in each of the two active sites</scene> of the dimer contribute directly to the chemistry of catalysis. Focusing on a single active site in the closed conformation, one can easily observe that <scene name='Citrate_Synthase/5ctsactivesiteresidues/10'>these three side chains and the two substrates are together</scene> in an arrangement favorable for reaction. (By contrast, <scene name='Citrate_Synthase/Activesite1ctsto2cts/12'>the active site residues are significantly farther apart</scene> in the open conformation; the difference in the distance is ~5Å along the axis that changes the most during the conformation shift.) {{Link Toggle AnimationOnPause}} | ||
The reaction mechanism for citrate synthase was proposed by Remington and colleagues<ref name="1cts">PMID:7120407</ref><ref>PMID: 2337600</ref> and is illustrated here in three dimensions using structures resembling key states of the reaction<ref>[[5cts]] as the state preceding condensation with oxaloacetate and a non-reactive version of acetyl-CoA bound, [[6cts]] as the state containing the bound intermediate, and [[3cts]] as the complex with the products. Positions of hydrogens on the ligands were calculated and added back to structures in the reaction scheme for instructional purposes and are not present in the experimentally-determined structures; additionally, arrows are drawn with atoms of the analog of acetyl-CoA to approximate the position of the reactive groups only as the reactive groups are not actually part of the analog or the molecules would have reacted; please, see the reaction scheme on this page for a more thorough accounting of the chemistry.</ref>. In this mechanism, three ionizable side chains in the active site of citrate synthase participate in acid-base catalysis: <scene name='Citrate_Synthase/5ctsactivesiteresidues/10'>His 274, His 320, and Asp 375</scene>. Citrate synthase is among one of the few enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors.<br> | The reaction mechanism for citrate synthase was proposed by Remington and colleagues<ref name="1cts">PMID:7120407</ref><ref>PMID: 2337600</ref> and is illustrated here in three dimensions using structures resembling key states of the reaction<ref>[[5cts]] as the state preceding condensation with oxaloacetate and a non-reactive version of acetyl-CoA bound, [[6cts]] as the state containing the bound intermediate, and [[3cts]] as the complex with the products. Positions of hydrogens on the ligands were calculated and added back to structures in the reaction scheme for instructional purposes and are not present in the experimentally-determined structures; additionally, arrows are drawn with atoms of the analog of acetyl-CoA to approximate the position of the reactive groups only as the reactive groups are not actually part of the analog or the molecules would have reacted; please, see the reaction scheme on this page for a more thorough accounting of the chemistry.</ref>. In this mechanism, three ionizable side chains in the active site of citrate synthase participate in acid-base catalysis: <scene name='Citrate_Synthase/5ctsactivesiteresidues/10'>His 274, His 320, and Asp 375</scene>. Citrate synthase is among one of the few enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors.<br> | ||
