File:1nek.mmol

2010-03-01T18:17:05Z

Michael Vick:

File:QuinoneMechanism.gif

2010-03-01T17:02:38Z

Michael Vick: uploaded a new version of "Image:QuinoneMechanism.gif": Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)

== Summary ==
Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)
== Licensing ==
{{subst:autodate|AutoReplaceable fair use people}}

Succinate Dehydrogenase

2010-03-01T17:00:30Z

Michael Vick:

==Succinate Dehydrogenase==
Succinate dehydrogenase (PDB = [[2wdv]] with empty ubiquinone binding site; PBD = [[1nek]] with ubiquinone bound), also called succinate-coenzyme Q reductase (SQR) or Complex II, is a tetrameric enzyme found in the cell membrane of some bacteria and the inner mitochondrial membrane of mammalian cells. It is classified as an α+β protein, as it contains segregated regions of α helices and antiparallel β sheets. It is involved in two aspects of digestion; it catalyzes the oxidation of succinate to fumarate in the citric acid cycle by simultaneously reducing ubiquinone to ubiquinol in the electron transport chain <ref>PMID:14672929</ref>.
{{STRUCTURE_2wdv | PDB=2wdv | SCENE= }}

===Structure:===

The tetramer is composed of two hydrophilic and two hydrophobic subunits. The hydrophilic subunits are named SdhA and SdhB; the former is a flavoprotein containing a covalently-bound FAD cofactor a binding site for succinate, while the latter is Fe-S protein bearing the three iron-sulfur clusters 2Fe-2S, 3Fe-4S, and 4Fe-4S. The hydrophobic subunits, termed SdhC and SdhD, anchor the protein in the mitochondrial membrane and formally comprise cytochrome b <ref>PMID:12966066</ref> and <ref>PMID:12560550</ref>. This cytochrome contains six transmembrane α-helices, a heme b group, and a binding site for ubiquinone located in a space bounded by SdhB, SdhC, and SdhD <ref>PMID:12560550</ref> and <ref>PMID:16407191</ref>.

{{STRUCTURE_1nek | PDB=1nek | SCENE= }}

===Binding sites:===

====Succinate====
The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. Residues Thr254, His354, and Arg399 stabilize the substrate with hydrogen bonding, while FAD removes the electrons and carries them to the first iron-sulfur cluster, 2Fe-2S, of SdhB <ref>PMID:235539</ref>. During this transfer, FAD is reduced to FADH2 <ref>ISBN:978-0-470-12930-2</ref>

====Ubiquinone====
The binding site for ubiquinone, in which the substrate is reduced to ubiquinol, is bordered by subunits B, C, and D. Residues His207 of SdhB, Ser27 and Arg31 of SdhC, and Tyr83 of SdhD stabilize ubiquinone, while residues Pro160, Trp163, Trp164, and Ile209 of SdhB and Ser27 and Ile28 of SdhC provide the necessary hydrophobic environment that stabilizes the ring <ref>PMID:16407191</ref>.

===Mechanisms:===

====Succinate oxidation====
The exact mechanism for the oxidation of succinate to fumarate has not yet been elucidated. The initial deprotonation may be performed by FAD, Glu255, Arg286, or His242 of SdhA, and the following elimination may be a concerted E2 or E1cb elimination. In the concerted mechanism, the α-carbon is deprotonated by a base as FAD removes a hydride from the β-carbon; this is shown in image 1 <ref>PMID:16950775</ref>.

[[Image:S.D.Oxidation_of_Succinate_E2.gif]]

Image 1: Oxidation of succinate to fumarate through E2 elimination

In the proposed E1cb mechanism, the deprotonation leads to the formation of an enolate intermediate; FAD then removes the hydride, as shown in Image 2 <ref>PMID:16950775</ref>.

[[Image:S.D.Oxidation_of_Succinate_E1cb.gif]]

Image 2: Oxidation of succinate to fumarate via E1cb elimination

====Ubiquinone reduction====
Ubiquinone is initially oriented in the active site such that the O1 carbonyl group interacts with Tyr83 of SdhD via hydrogen bonding. The electrons removed during the oxidation reaction are conveyed through the iron-sulfur clusters to 3Fe-4S; their presence on that cluster stimulates the substrate to reorient so that a second hydrogen bond between the O4 carbonyl group and Ser27 of SdhC may form. The electrons are transferred to the substrate individually, with the addition of the first producing a radical semiquinone and the second completing the reduction to ubiquinol. This mechanism is illustrated in image 3 <ref>PMID:16950775</ref>.

[[Image:QuinoneMechanism.gif]]

Image 3: Reduction of ubiquinone to ubiquinol

===References:===
<references/>

File:QuinoneMechanism.gif

2010-03-01T16:59:17Z

Michael Vick: uploaded a new version of "Image:QuinoneMechanism.gif": Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)

== Summary ==
Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)
== Licensing ==
{{subst:autodate|AutoReplaceable fair use people}}

File:QuinoneMechanism.gif

2010-03-01T16:57:49Z

Michael Vick: Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)

== Summary ==
Image 3: Reduction of ubiquinone to ubiquinol (from Wikimedia Commons)
== Licensing ==
{{subst:autodate|AutoReplaceable fair use people}}

File:S.D.Oxidation of Succinate E1cb.gif

2010-03-01T16:57:03Z

Michael Vick: Image 2: Oxidation of succinate to fumarate via E1cb elimination (from Wikimedia Commons)

== Summary ==
Image 2: Oxidation of succinate to fumarate via E1cb elimination (from Wikimedia Commons)
== Licensing ==
{{subst:autodate|AutoReplaceable fair use people}}

Succinate Dehydrogenase

2010-03-01T16:56:20Z

Michael Vick:

==Succinate Dehydrogenase==
Succinate dehydrogenase (PDB = [[2wdv]] with empty ubiquinone binding site; PBD = [[1nek]] with ubiquinone bound), also called succinate-coenzyme Q reductase (SQR) or Complex II, is a tetrameric enzyme found in the cell membrane of some bacteria and the inner mitochondrial membrane of mammalian cells. It is classified as an α+β protein, as it contains segregated regions of α helices and antiparallel β sheets. It is involved in two aspects of digestion; it catalyzes the oxidation of succinate to fumarate in the citric acid cycle by simultaneously reducing ubiquinone to ubiquinol in the electron transport chain <ref>PMID:14672929</ref>.
{{STRUCTURE_2wdv | PDB=2wdv | SCENE= }}

===Structure:===

The tetramer is composed of two hydrophilic and two hydrophobic subunits. The hydrophilic subunits are named SdhA and SdhB; the former is a flavoprotein containing a covalently-bound FAD cofactor a binding site for succinate, while the latter is Fe-S protein bearing the three iron-sulfur clusters 2Fe-2S, 3Fe-4S, and 4Fe-4S. The hydrophobic subunits, termed SdhC and SdhD, anchor the protein in the mitochondrial membrane and formally comprise cytochrome b <ref>PMID:12966066</ref> and <ref>PMID:12560550</ref>. This cytochrome contains six transmembrane α-helices, a heme b group, and a binding site for ubiquinone located in a space bounded by SdhB, SdhC, and SdhD <ref>PMID:12560550</ref> and <ref>PMID:16407191</ref>.

{{STRUCTURE_1nek | PDB=1nek | SCENE= }}

===Binding sites:===

====Succinate====
The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. Residues Thr254, His354, and Arg399 stabilize the substrate with hydrogen bonding, while FAD removes the electrons and carries them to the first iron-sulfur cluster, 2Fe-2S, of SdhB <ref>PMID:235539</ref>. During this transfer, FAD is reduced to FADH2 <ref>ISBN:978-0-470-12930-2</ref>

====Ubiquinone====
The binding site for ubiquinone, in which the substrate is reduced to ubiquinol, is bordered by subunits B, C, and D. Residues His207 of SdhB, Ser27 and Arg31 of SdhC, and Tyr83 of SdhD stabilize ubiquinone, while residues Pro160, Trp163, Trp164, and Ile209 of SdhB and Ser27 and Ile28 of SdhC provide the necessary hydrophobic environment that stabilizes the ring <ref>PMID:16407191</ref>.

===Mechanisms:===

====Succinate oxidation====
The exact mechanism for the oxidation of succinate to fumarate has not yet been elucidated. The initial deprotonation may be performed by FAD, Glu255, Arg286, or His242 of SdhA, and the following elimination may be a concerted E2 or E1cb elimination. In the concerted mechanism, the α-carbon is deprotonated by a base as FAD removes a hydride from the β-carbon; this is shown in image 1 [8].

[[Image:S.D.Oxidation_of_Succinate_E2.gif]]

Image 1: Oxidation of succinate to fumarate through E2 elimination

In the proposed E1cb mechanism, the deprotonation leads to the formation of an enolate intermediate; FAD then removes the hydride, as shown in Image 2 [8].

[[Image:S.D.Oxidation_of_Succinate_E1cb.gif]]

Image 2: Oxidation of succinate to fumarate via E1cb elimination

====Ubiquinone reduction====
Ubiquinone is initially oriented in the active site such that the O1 carbonyl group interacts with Tyr83 of SdhD via hydrogen bonding. The electrons removed during the oxidation reaction are conveyed through the iron-sulfur clusters to 3Fe-4S; their presence on that cluster stimulates the substrate to reorient so that a second hydrogen bond between the O4 carbonyl group and Ser27 of SdhC may form. The electrons are transferred to the substrate individually, with the addition of the first producing a radical semiquinone and the second completing the reduction to ubiquinol. This mechanism is illustrated in image 3 [8].

[[Image:QuinoneMechanism.gif]]

Image 3: Reduction of ubiquinone to ubiquinol

===References:===
<references/>

File:S.D.Oxidation of Succinate E2.gif

2010-03-01T16:53:16Z

2010-03-01T02:06:50Z

Michael Vick:

==Succinate Dehydrogenase==
Succinate dehydrogenase (PDB = 2wdv with empty ubiquinone binding site; PBD = 1nek with ubiquinone bound), also called succinate-coenzyme Q reductase (SQR) or Complex II, is a tetrameric enzyme found in the cell membrane of some bacteria and the inner mitochondrial membrane of mammalian cells. It is classified as an α+β protein, as it contains segregated regions of α helices and antiparallel β sheets. It is involved in two aspects of digestion; it catalyzes the oxidation of succinate to fumarate in the citric acid cycle by simultaneously reducing ubiquinone to ubiquinol in the electron transport chain [1].

{{STRUCTURE_2wdv | PDB=2wdv | SCENE= }}

'''Structure:'''
The tetramer is composed of two hydrophilic and two hydrophobic subunits. The hydrophilic subunits are named SdhA and SdhB; the former is a flavoprotein containing a covalently-bound FAD cofactor a binding site for succinate, while the latter is Fe-S protein bearing the three iron-sulfur clusters 2Fe-2S, 3Fe-4S, and 4Fe-4S. The hydrophobic subunits, termed SdhC and SdhD, anchor the protein in the mitochondrial membrane and formally comprise cytochrome b [3] and [4]. This cytochrome contains six transmembrane α-helices, a heme b group, and a binding site for ubiquinone located in a space bounded by SdhB, SdhC, and SdhD [4] and [5].

'''Binding sites:'''
''Succinate'' – The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. Residues Thr254, His354, and Arg399 stabilize the substrate with hydrogen bonding, while FAD removes the electrons and carries them to the first iron-sulfur cluster, 2Fe-2S, of SdhB [6]. During this transfer, FAD is reduced to FADH2 [7].

''Ubiquinone'' – The binding site for ubiquinone, in which the substrate is reduced to ubiquinol, is bordered by subunits B, C, and D. Residues His207 of SdhB, Ser27 and Arg31 of SdhC, and Tyr83 of SdhD stabilize ubiquinone, while residues Pro160, Trp163, Trp164, and Ile209 of SdhB and Ser27 and Ile28 of SdhC provide the necessary hydrophobic environment that stabilizes the ring [5].

{{STRUCTURE_1nek | PDB=1nek | SCENE= }}

Succinate Dehydrogenase

2010-03-01T02:05:37Z

Michael Vick: New page: ==Succinate Dehydrogenase== Succinate dehydrogenase (PDB = 2wdv with empty ubiquinone binding site; PBD = 1nek with ubiquinone bound), also called succinate-coenzyme Q reductase (SQR) or C...

Michael Vick Sandbox 1

2010-02-19T14:55:12Z

Michael Vick: /* The Mechanism of Trypsin */

==The Mechanism of Trypsin==

{{STRUCTURE_2ah4| PDB=2ah4 | SCENE= }}

The secondary structure of trypsin (pdb code [[2ah4]]) is composed of 13 antiparallel beta sheets with three alpha helices interspersed throughout. The sheets are divided into two groups—one with six sheets, and one with seven—each forming a tight barrel that appears relatively open on each end <ref>PMID:16636277</ref>. The three members of the catalytic triad in other serine proteases—His 57, Asp 102, and Ser 195—are located near one end of the group of six beta sheets “capped” by an alpha helix. This is logical, as the three work together to stabilize the scissile bond of residues with small side chains. His 57 and Asp 102, which both serve to stabilize via hydrogen bonding and as proton acceptors, lie outside the barrel proper. Serine 195, which forms the tetrahedral intermediate and “hydrolyzes” the peptide bond, also formally lies outside this barrel, but is placed such that it is able to easily interact with any peptide chain which passes through either barrel. Although it seems difficult to imagine how a peptide chain could fit within the relatively small barrels, the ability of certain “flaps” to move and open up the barrels—as in HIV protease—provides a possible explanation for this problem.

<references/>

Michael Vick Sandbox 1

2010-02-19T14:51:43Z

Michael Vick: /* The Mechanism of Trypsin */

==The Mechanism of Trypsin==

{{STRUCTURE_2ah4| PDB=2ah4 | SCENE= }}

The secondary structure of trypsin (pdb code [[2ah4]]) is composed of 13 antiparallel beta sheets with three alpha helices interspersed throughout. The sheets are divided into two groups—one with six sheets, and one with seven—each forming a tight barrel that appears relatively open on each end. The three members of the catalytic triad in other serine proteases—His 57, Asp 102, and Ser 195—are located near one end of the group of six beta sheets “capped” by an alpha helix. This is logical, as the three work together to stabilize the scissile bond of residues with small side chains. His 57 and Asp 102, which both serve to stabilize via hydrogen bonding and as proton acceptors, lie outside the barrel proper. Serine 195, which forms the tetrahedral intermediate and “hydrolyzes” the peptide bond, also formally lies outside this barrel, but is placed such that it is able to easily interact with any peptide chain which passes through either barrel. Although it seems difficult to imagine how a peptide chain could fit within the relatively small barrels, the ability of certain “flaps” to move and open up the barrels—as in HIV protease—provides a possible explanation for this problem.