Sandbox 160: Difference between revisions

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== Structure & Function ==

Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)has carefully been studied in a number of bacterial, parasitic and mammalian species and it has been found that it exists as homotetrameric protein <ref name="reference 1"/>. Two anion binding sites have been found where the two phosphates involved in the reaction will be bound during catalysis. One site is labeled "Pi" and is the location where the inorganic phosphate involved will bind and the other has been labeled "Ps" which is where the C-3 ~~phospahte~~ of Gylceraldeyhde 3-Phosphate will bind <ref name="reference 1"/> .

Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)has carefully been studied in a number of bacterial, parasitic and mammalian species and it has been found that it exists as homotetrameric protein <ref name="reference 1"/>. Two anion binding sites have been found where the two phosphates involved in the reaction will be bound during catalysis. One site is labeled "Pi" and is the location where the inorganic phosphate involved will bind and the other has been labeled "Ps" which is where the C-3 phosphate of Gylceraldeyhde 3-Phosphate will bind <ref name="reference 1"/> . Further experimentation has shown that the "Ps" site has been conserved in numerous GAPDH complexes and the the former may involve two possible sites.

The enzyme contains a functional NAD+ group which functions as a hydrogen acceptor during the course of the reaction which is bound to a Rossman fold. During the catalysis of glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate a hydride ion is enzymatically transferred from the aldehyde group of glyceraldehyde 3-phosphate to the nicotinamide ring of NAD+ reducing it to NADH (pink)<ref name="reference 1">19243605 </ref>. The active site of GAPDH contains a cysteine (Cys149 colored green) residue which reacts with the glyceraldehyde 3-phosphate molecule through its -SH group. The substrate is covalently bound during the reaction through its aldehyde group to the -SH group of the cysteine residue and the resulting reaction produces a thiohemiacetal intermediate <ref name="reference 1"/>. Note that this reaction occurs through acid base catalysis with aid of a histidine residue (His176).The <scene name='Sandbox_160/Newscene/1'>active site</scene> of the molecule is illustrated to the right.

The enzyme contains a functional NAD+ group which functions as a hydrogen acceptor during the course of the reaction which is bound to a Rossman fold. During the catalysis of glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate a hydride ion is enzymatically transferred from the aldehyde group of glyceraldehyde 3-phosphate to the nicotinamide ring of NAD+ reducing it to NADH (pink)<ref name="reference 1">PMID:19243605 </ref>. The active site of GAPDH contains a cysteine (Cys149 colored green) residue which reacts with the glyceraldehyde 3-phosphate molecule through its -SH group. The substrate is covalently bound during the reaction through its aldehyde group to the -SH group of the cysteine residue and the resulting reaction produces a thiohemiacetal intermediate <ref name="reference 1"/>. Note that this reaction occurs through acid base catalysis with aid of a histidine residue (His176).The <scene name='Sandbox_160/Newscene/1'>active site</scene> of the molecule is illustrated to the right.

A simplified illustration of the net reaction is as follows:

Line 14:

The Pi that is involved in the reaction functions to attack by phosphorolysis the thioester intermediate that is formed by the substrate on the cysteine reside after NAD+ has been reduced <ref name="reference 1"/>. The attack by Pi on the carbonyl carbon of C1 is simultaneously followed by the replacement of bound NADH for NAD+ so another turn of the cycle can now commence. The final product is released as 1,3 bisphosphoglycerate in which the second Pi molecule has been incorporated.

<ref name="reference 2">PMID:11846565 </ref>.

Sandbox 160: Difference between revisions

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@@ Line 5: / Line 5: @@
 == Structure & Function ==
-Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)has carefully been studied in a number of bacterial, parasitic and mammalian species and it has been found that it exists as homotetrameric protein <ref name="reference 1"/>. Two anion binding sites have been found where the two phosphates involved in the reaction will be bound during catalysis. One site is labeled "Pi" and is the location where the inorganic phosphate involved will bind and the other has been labeled "Ps" which is where the C-3 phospahte of Gylceraldeyhde 3-Phosphate will bind <ref name="reference 1"/> .
+Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH)has carefully been studied in a number of bacterial, parasitic and mammalian species and it has been found that it exists as homotetrameric protein <ref name="reference 1"/>. Two anion binding sites have been found where the two phosphates involved in the reaction will be bound during catalysis. One site is labeled "Pi" and is the location where the inorganic phosphate involved will bind and the other has been labeled "Ps" which is where the C-3 phosphate of Gylceraldeyhde 3-Phosphate will bind <ref name="reference 1"/> . Further experimentation has shown that the "Ps" site has been conserved in numerous GAPDH complexes and the the former may involve two possible sites.
-The enzyme contains a functional NAD+ group which functions as a hydrogen acceptor during the course of the reaction which is bound to a Rossman fold. During the catalysis of glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate a hydride ion is enzymatically transferred from the aldehyde group of glyceraldehyde 3-phosphate to the nicotinamide ring of NAD+ reducing it to NADH (pink)<ref name="reference 1">19243605 </ref>. The active site of GAPDH contains a cysteine (Cys149 colored green) residue which reacts with the glyceraldehyde 3-phosphate molecule through its -SH group. The substrate is covalently bound during the reaction through its aldehyde group to the -SH group of the cysteine residue and the resulting reaction produces a thiohemiacetal intermediate <ref name="reference 1"/>. Note that this reaction occurs through acid base catalysis with aid of a histidine residue (His176).The <scene name='Sandbox_160/Newscene/1'>active site</scene> of the molecule is illustrated to the right.
+The enzyme contains a functional NAD+ group which functions as a hydrogen acceptor during the course of the reaction which is bound to a Rossman fold. During the catalysis of glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate a hydride ion is enzymatically transferred from the aldehyde group of glyceraldehyde 3-phosphate to the nicotinamide ring of NAD+ reducing it to NADH (pink)<ref name="reference 1">PMID:19243605 </ref>. The active site of GAPDH contains a cysteine (Cys149 colored green) residue which reacts with the glyceraldehyde 3-phosphate molecule through its -SH group. The substrate is covalently bound during the reaction through its aldehyde group to the -SH group of the cysteine residue and the resulting reaction produces a thiohemiacetal intermediate <ref name="reference 1"/>. Note that this reaction occurs through acid base catalysis with aid of a histidine residue (His176).The <scene name='Sandbox_160/Newscene/1'>active site</scene> of the molecule is illustrated to the right.
 A simplified illustration of the net reaction is as follows:
@@ Line 14: / Line 14: @@
 The Pi that is involved in the reaction functions to attack by phosphorolysis the thioester intermediate that is formed by the substrate on the cysteine reside after NAD+ has been reduced <ref name="reference 1"/>. The attack by Pi on the carbonyl carbon of C1 is simultaneously followed by the replacement of bound NADH for NAD+ so another turn of the cycle can now commence. The final product is released as 1,3 bisphosphoglycerate in which the second Pi molecule has been incorporated.
+<ref name="reference 2">PMID:11846565 </ref>.