Proteopedia - User contributions [en]

Succinyl-CoA synthetase

2010-04-22T23:25:53Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''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. It is the fifth step in the citric acid cycle.

==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>
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>

==Mechanism==
The histidine residue involved in the (de)phosphorylation of (ATP)ADP acts through the following mechanism.
[[Image:Synthetase_mechanism.jpg]]

A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site.<ref>PMID:6997289</ref> It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a complex containing 2 ATP residues as well as 2 phosphoric acid residues, after incubation this the complex converts to another one containing 4 phosphoric residues per protein. Only the second complex reacts with succinate and CoA to form the succinyl-CoA complex which then releases as many phosphoric residues as bound succinate.<ref>PMID:570066</ref> A transfer of the phosphoric residue from the first active site is seen to be coordinate with a transfer of a phosphoric residue to the second active site suggesting again a cooperative binding catalysis. This cooperative catalysis means that the presence of ATP or ADP can be both activating and inhibiting depending on the stage of catalysis they interact with the enzyme.

After the Succinyl-CoA has been phosphorylated and subsequently dephosphorylated it is release as succinate which continues along the Krebs cycle.

==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='300' frame='true' align='right' caption='Succinyl-CoA synthetase'/>

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.

==Kinetics==
As stated earlier, the presence of GTP, GDP, ATP, and ADP can be either activating or inhibiting depending on the stage of catalysis it interacts with the enzyme.

==Regulation==
Succinyl-CoA synthetase is not a major regulator in the Krebs cycle, making it dependent on the steps prior.

<references/>

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-04-22T23:17:23Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''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.

==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>
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>

==Mechanism==
The histidine residue involved in the (de)phosphorylation of (ATP)ADP acts through the following mechanism.
[[Image:Synthetase_mechanism.jpg]]
A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site.<ref>PMID:6997289</ref> It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a complex containing 2 ATP residues as well as 2 phosphoric acid residues, after incubation this the complex converts to another one containing 4 phosphoric residues per protein. Only the second complex reacts with succinate and CoA to form the succinyl-CoA complex which then releases as many phosphoric residues as bound succinate.<ref>PMID:570066</ref> A transfer of the phosphoric residue from the first active site is seen to be coordinate with a transfer of a phosphoric residue to the second active site suggesting again a cooperative binding catalysis. This cooperative catalysis means that the presence of ATP or ADP can be both activating and inhibiting depending on the stage of catalysis they interact with the enzyme.

==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='300' frame='true' align='right' caption='Succinyl-CoA synthetase'/>

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.

<references/>

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-04-22T23:11:32Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''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.

==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>
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>

==Mechanism==
The histidine residue involved in the (de)phosphorylation of (ATP)ADP acts through the following mechanism.
[[Image:Example.jpg]]
A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site.<ref>PMID:6997289</ref> It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a complex containing 2 ATP residues as well as 2 phosphoric acid residues, after incubation this the complex converts to another one containing 4 phosphoric residues per protein. Only the second complex reacts with succinate and CoA to form the succinyl-CoA complex which then releases as many phosphoric residues as bound succinate.<ref>PMID:570066</ref> A transfer of the phosphoric residue from the first active site is seen to be coordinate with a transfer of a phosphoric residue to the second active site suggesting again a cooperative binding catalysis. This cooperative catalysis means that the presence of ATP or ADP can be both activating and inhibiting depending on the stage of catalysis they interact with the enzyme.

==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='300' frame='true' align='right' caption='Succinyl-CoA synthetase'/>

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.

<references/>

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-03-22T04:53:28Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''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.

==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>
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>

==Mechanism==
A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site.<ref>PMID:6997289</ref> It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a complex containing 2 ATP residues as well as 2 phosphoric acid residues, after incubation this the complex converts to another one containing 4 phosphoric residues per protein. Only the second complex reacts with succinate and CoA to form the succinyl-CoA complex which then releases as many phosphoric residues as bound succinate.<ref>PMID:570066</ref> A transfer of the phosphoric residue from the first active site is seen to be coordinate with a transfer of a phosphoric residue to the second active site suggesting again a cooperative binding catalysis. This cooperative catalysis means that the presence of ATP or ADP can be both activating and inhibiting depending on the stage of catalysis they interact with the enzyme.

==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='300' frame='true' align='right' caption='Succinyl-CoA synthetase'/>

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.

<references/>

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-03-22T04:46:04Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''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.

==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>
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 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>

==Mechanism==
A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site.<ref>PMID:6997289</ref> It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a complex containing 2 ATP residues as well as 2 phosphoric acid residues, after incubation this the complex converts to another one containing 4 phosphoric residues per protein. Only the second complex reacts with succinate and CoA to form the succinyl-CoA complex which then releases as many phosphoric residues as bound succinate.<ref>PMID:570066</ref>

==Bound Form of Succinyl-CoA synthetase==
<applet load='1cqi' size='300' frame='true' align='right' caption='Succinyl-CoA synthetase'/>

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.

<references/>

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-03-01T20:11:54Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-03-01T20:07:45Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-03-01T20:07:15Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-03-01T20:06:21Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-03-01T03:10:05Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-03-01T01:56:05Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T20:59:01Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T20:27:14Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T20:20:54Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T20:09:41Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T08:31:06Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T07:45:09Z

Lucas Hamlow:

<applet load='1cqj' size='300' frame='true' align='right' caption='Structure of succinyl-CoA synthetase' />

'''Succinyl-Coa synthetase''' catalyzes the reversible reaction of succinyl-CoA + ADP + Pi <-> succinate + CoA + ATP.

==Structure==
'''Succinyl-CoA synthetase''' is a tetramer with an active site on each dimer. This can be seen in the Jmol representation (the PDB code is 1CQJ).

==Trypsin-BPTI complex==
The trypsin backbone is shown in pink and the trypsin inhibitor, BPTI, in yellow (PDB code [[2ptc]]). The <scene name='Serine_Protease/Active_site/3'>active site</scene> residues [Ser195-His57-Asp102-Ser214] are shown in green, the disulfide bond between residues 14-38 is shown in yellow and the Lys 15 sidechain at the specificity site in pink.

{{Clear}}
== '''Content Donators''' ==

Succinyl-CoA synthetase

2010-02-28T07:10:07Z

Lucas Hamlow:

Succinyl-CoA synthetase

2010-02-28T05:49:43Z

Lucas Hamlow:

<applet load="1ppb" size="350" color="white" frame="true" align="left" spinBox="true"
caption="Human Thrombin with PPACK inhibitor" />

'''Succinyl-Coa synthetase''' catalyzes the reversible reaction of succinyl-CoA + ADP + Pi <-> succinate + CoA + ATP.

==Thrombin==
'''Thrombin''' is a "trypsin-like" serine protease. Its structure (PDB code [[1ppb]]) is shown here with a peptide chloroketone inhibitor (PPACK). The thrombin A chain (cleaved N terminal fragement) is shown in cyan and the B chain is shown in red. The <scene name='Serine_Protease/Active_site/2'>Active site</scene> is made up of a catalytic triad of Ser195, His57 and Asp102, backed up by Ser214. The peptide chloroketone inhibitor (PPACK) is shown in purple. A closeup shows the <scene name='Serine_Protease/Activation_site/2'>activation site</scene> at which the sidechain of Asp194 makes a salt link with the N-terminus at residue 16, newly formed when the A chain is cleaved in the zymogen-to-enzyme activation process. The specificity pocket is on one side of the throat of the domain 2 beta barrel, and the activation site is close next to it.

The B chain consists of <scene name='Serine_Protease/Domains/1'>two domains</scene>. As is true for all of the "trypsin-like" serine proteases, each of the two thrombin domains consists mainly of a 6-stranded, antiparallel beta barrel. The specificity pocket (here filled with the Lys sidechain of the PPACK inhibitor) is in one side of the throat of the domain 2beta barrel, and the activation site is close next to it.

<applet load="2ptc" size="350" color="white" frame="true" align="right" spinBox="true"
caption="Trypsin BPT1 complex" />

==Trypsin-BPTI complex==
The trypsin backbone is shown in pink and the trypsin inhibitor, BPTI, in yellow (PDB code [[2ptc]]). The <scene name='Serine_Protease/Active_site/3'>active site</scene> residues [Ser195-His57-Asp102-Ser214] are shown in green, the disulfide bond between residues 14-38 is shown in yellow and the Lys 15 sidechain at the specificity site in pink.

{{Clear}}
== '''Content Donators''' ==

* Content for this page has been included and adapted with permission from Jane S. and David C. Richardson's http://kinemage.biochem.duke.edu/

Succinyl-CoA synthetase

2010-02-28T05:43:58Z

Lucas Hamlow: New page: <applet load="1ppb" size="350" color="white" frame="true" align="left" spinBox="true" caption="Human Thrombin with PPACK inhibitor" /> '''Serine proteases''', or '''proteinases''', so ca...

<applet load="1ppb" size="350" color="white" frame="true" align="left" spinBox="true"
caption="Human Thrombin with PPACK inhibitor" />

'''Serine proteases''', or '''proteinases''', so called due to the presence of a serine residue in the active site, are a class of enzymes that catalyse the hydrolysis of peptide bonds in proteins.

==Thrombin==
'''Thrombin''' is a "trypsin-like" serine protease. Its structure (PDB code [[1ppb]]) is shown here with a peptide chloroketone inhibitor (PPACK). The thrombin A chain (cleaved N terminal fragement) is shown in cyan and the B chain is shown in red. The <scene name='Serine_Protease/Active_site/2'>Active site</scene> is made up of a catalytic triad of Ser195, His57 and Asp102, backed up by Ser214. The peptide chloroketone inhibitor (PPACK) is shown in purple. A closeup shows the <scene name='Serine_Protease/Activation_site/2'>activation site</scene> at which the sidechain of Asp194 makes a salt link with the N-terminus at residue 16, newly formed when the A chain is cleaved in the zymogen-to-enzyme activation process. The specificity pocket is on one side of the throat of the domain 2 beta barrel, and the activation site is close next to it.

The B chain consists of <scene name='Serine_Protease/Domains/1'>two domains</scene>. As is true for all of the "trypsin-like" serine proteases, each of the two thrombin domains consists mainly of a 6-stranded, antiparallel beta barrel. The specificity pocket (here filled with the Lys sidechain of the PPACK inhibitor) is in one side of the throat of the domain 2beta barrel, and the activation site is close next to it.

<applet load="2ptc" size="350" color="white" frame="true" align="right" spinBox="true"
caption="Trypsin BPT1 complex" />

==Trypsin-BPTI complex==
The trypsin backbone is shown in pink and the trypsin inhibitor, BPTI, in yellow (PDB code [[2ptc]]). The <scene name='Serine_Protease/Active_site/3'>active site</scene> residues [Ser195-His57-Asp102-Ser214] are shown in green, the disulfide bond between residues 14-38 is shown in yellow and the Lys 15 sidechain at the specificity site in pink.

{{Clear}}
== '''Content Donators''' ==

* Content for this page has been included and adapted with permission from Jane S. and David C. Richardson's http://kinemage.biochem.duke.edu/