Succinyl-CoA synthetase: Difference between revisions

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<applet load='1cqj' size='400' frame='true' align='right' caption='Structure of E. coli succinyl-CoA synthetase α and β chains complex with phosphate and CoA [[1cqj]]' />
<StructureSection load='1cqj' size='350' side='right' scene='' caption='E. coli succinyl-CoA synthetase α subunit (grey, yellow) and β subunit (green, magenta) complex with CoA and phosphate (PDB code [[1cqj]])'>


'''Succinyl-Coa synthetase''' catalyzes the reversible reaction of succinyl-CoA + NDP + Pi <-> succinate + CoA + NTP (where N is either adenosine or guanosine. It can be found in Escherichia coli and is the fifth step in the citric acid cycle. Due to its involvement in the citric acid cycle it is very important in all living cells that use oxygen as a part of cellular respiration. This entire process (Citric acid cycle) is necessary in producing one GTP or ATP, three NADHs, and two carbon dioxides.
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==Function==
 
'''Succinyl-CoA synthetase''' or '''succinate-CoA ligase''' catalyzes the reversible reaction of succinyl-CoA + NDP + Pi <-> succinate + CoA + NTP (where N is either adenosine or guanosine. It can be found in Escherichia coli and is the fifth step in the [[Citric Acid Cycle|citric acid cycle]]. Due to its involvement in the citric acid cycle it is very important in all living cells that use oxygen as a part of cellular respiration. This entire process (Citric acid cycle) is necessary in producing one GTP or ATP, three NADHs, and two carbon dioxides. See also:<br />
*[[Krebs cycle carbons]]
*[[Krebs cycle importance]]
*[[Krebs cycle overview]]
*[[Krebs cycle reactions]]
*[[Citric Acid Cycle]]
*[[Krebs cycle step 5]]


==Structure==
==Structure==
'''Succinyl-CoA synthetase''' is a tetramer with an active site on each subunit. This can be seen in the Jmol representation (the PDB code is 1CQJ). The two subunits are denoted alpha and beta. A phosphorylated histidine intermediate <scene name='Lucas_Hamlow_sandbox_1/Active_histidine_residue/1'>(HIS 246 alpha)</scene> is responsible for the dephosphorylation of ATP and it is suspected that there is another active site on the beta subunit that is responsible for the continued catalysis of the reaction. There is a suspected nucleotide binding site on the N-terminal of the beta subunit which would imply that there are two active sites roughly 35 A apart from each other and that the HIS 246 alpha loop moves between them during catalysis.<ref>PMID:10353839</ref>   
'''Succinyl-CoA synthetase''' or '''Succinyl-CoA ligase''' is a tetramer with an active site on each subunit. This can be seen in the Jmol representation (the PDB code is 1CQJ). The two subunits are denoted alpha and beta. A phosphorylated histidine intermediate <scene name='Lucas_Hamlow_sandbox_1/Active_histidine_residue/1'>(HIS 246 alpha)</scene> is responsible for the dephosphorylation of ATP and it is suspected that there is another active site on the beta subunit that is responsible for the continued catalysis of the reaction. There is a suspected nucleotide binding site on the N-terminal of the beta subunit which would imply that there are two active sites roughly 35 A apart from each other and that the HIS 246 alpha loop moves between them during catalysis.<ref>PMID:10353839</ref>   
On the alpha subunit it has been shown that <scene name='Lucas_Hamlow_sandbox_1/Active_his_with_glu_208/1'>GLU 208 alpha</scene> interacts in some way with the active HIS 246 alpha residue in the phosphorylated and dephosphorylated enzyme and it is supposed that GLU 197 beta serves a similar purpose on the beta subunit.<ref>PMID:11781092</ref>
On the alpha subunit it has been shown that <scene name='Lucas_Hamlow_sandbox_1/Active_his_with_glu_208/1'>GLU 208 alpha</scene> interacts in some way with the active HIS 246 alpha residue in the phosphorylated and dephosphorylated enzyme and it is supposed that GLU 197 beta serves a similar purpose on the beta subunit.<ref>PMID:11781092</ref>


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==Bound Form of Succinyl-CoA synthetase==
==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='400' frame='true' align='right' caption='Structure of E. coli succinyl-CoA synthetase α and β chains complex with phosphate, Mg+2 ion, ADP and CoA [[1cqi]]'/>


The form of succinyl-CoA synthetase shown here (PDB code 1CQI) is the bound form with two <scene name='Lucas_Hamlow_sandbox_1/Adp-mg_complex/1'>ADP-Mg complexes</scene> (the ADP is highlighted and the Mg is in green).<ref>PMID:10625475</ref> As seen here, the <scene name='Lucas_Hamlow_sandbox_1/His_246_near_pi_group/1'>Histidine 246</scene> residues on both the alpha and beta subunits are present and interacting with the lone Pi group while the ADP group is bound elsewhere on the subunit.  
The form of succinyl-CoA synthetase shown here (PDB code 1CQI) is the bound form with two <scene name='Lucas_Hamlow_sandbox_1/Adp-mg_complex/1'>ADP-Mg complexes</scene> (the ADP is highlighted and the Mg is in green).<ref>PMID:10625475</ref> As seen here, the <scene name='Lucas_Hamlow_sandbox_1/His_246_near_pi_group/1'>Histidine 246</scene> residues on both the alpha and beta subunits are present and interacting with the lone Pi group while the ADP group is bound elsewhere on the subunit.  
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==3D structures of succinyl-CoA synthetase==
==3D structures of succinyl-CoA synthetase==
[[Succinyl-CoA synthetase 3D structures]]


===Histidine-phosphorylated succinyl-CoA synthetase===
</StructureSection>
 
[[1scu – EcSCS α+β subunit  – ''Escherichia coli''<br />
[[2nu6]], [[2nu7]], [[2nu8]], [[2nu9]], [[2nua]] - EcSCS α (mutant) + β subunit<br />
[[1eud – pSCS α+β (mutant) subunit - pig<br />
[[2fp4]] - pSCS α+β subunit  + Mg + GTP<br />
[[2fpi]], [[2fpp]] - pSCS α+β subunit 
===Dephosphorylated succinyl-CoA synthetase===
 
[[1cqi]] - EcSCS α+β subunit  + Mg + ADP + PO4<br />
[[1cqj]], [[1jkj]] - EcSCS α+β subunit + PO4<br />
[[1jll]] -  EcSCS α+β (mutant) subunit + PO4<br />
[[1euc – pSCS α+β (mutant) subunit + PO4<br />
[[2fpg – pSCS α+β subunit  + PO4 + GDP<br />
[[1oi7 – SCS α subunit (mutant) – ''Thermos thermophilus''<br />
[[2yv1]] - SCS α subunit – ''Methanocaldococcus jannaschii''<br />
[[2yv2]] - SCS α subunit – ''Aeropyrum pernix''


==Additional Resources==
==Additional Resources==
For Additional Information, See [[Carbohydrate Metabolism]] <br />
* [[Carbohydrate Metabolism]] <br />
* [[Krebs cycle step 5]]


==References==
==References==
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== '''Content Donators''' ==
== '''Content Donators''' ==
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Lucas Hamlow, David Canner, J.D. McClintic, Michal Harel, Wayne Decatur, Alexander Berchansky