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Glyceraldehyde-3-Phosphate Dehydrogenase: Difference between revisions

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{{STRUCTURE_3gpd |  PDB=3gpd  |  SCENE=  }}
{{STRUCTURE_3gpd |  PDB=3gpd  |  SCENE=  }}
{{STRUCTURE_3gpd|  PDB=3gpd  | SIZE=400| SCENE= |right|CAPTION=Human glyceraldehyde-3-phosphate dehydrogenase complex with NAD and sulfate, [[3gpd]] }}


== Function ==
== Function ==
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== Regulation ==
== Regulation ==
GAPDH is not a highly regulated step with in the glycolytic pathway because of relatively low energy transitions that occur between steps five and nine. However, there are a few items that must be present for the reaction to proceed. GAPDH is inactivated by the alkylation of iodoacetate, in which the Iodine inhibits the active site by binding to the Sulfur present in the cystine residue. If the active site is blocked by by an inhibitor such as Iodine then the reaction will stop. Also NAD oxidizes the GAP, so the availability of hydrogen and inorganic phosphates also could effect the rates of the reaction. The reason this step is not highly regulated is because Iodine is not present in the blood stream and the absence of both hydrogen and inorganic phosphates will cause the reaction to yield before this step is met.
GAPDH is not a highly regulated step with in the glycolytic pathway because of relatively low energy transitions that occur between steps five and nine. However, there are a few items that must be present for the reaction to proceed. GAPDH is inactivated by the alkylation of iodoacetate, in which the Iodine inhibits the active site by binding to the Sulfur present in the cystine residue. If the active site is blocked by by an inhibitor such as Iodine then the reaction will stop. Also NAD oxidizes the GAP, so the availability of hydrogen and inorganic phosphates also could effect the rates of the reaction. The reason this step is not highly regulated is because Iodine is not present in the blood stream and the absence of both hydrogen and inorganic phosphates will cause the reaction to yield before this step is met.


== Reaction Mechanism ==
== Reaction Mechanism ==
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For additional information, see: [[Carbohydrate Metabolism]]
For additional information, see: [[Carbohydrate Metabolism]]
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<br />
==3D structures of glyceraldehyde-3-phosphate dehydrogenase==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
===Apo GAPDH===
1vsu – CpGAPDH – ''Cryptosporidium parvum''<br />
1dc5 - EcGAPDH – ''Escherichia coli''<br />
1euh, 1qi6 - SmGAPDH – ''Streptococcus mutans''<br />
2hki – sGAPDH – spinach<br />
3e6a – RiGAPDH ligand binding domain – rice<br />
3lc7 - SaGAPDH – ''Staphylococcus aureus''<br />
3pqa – MjGAPDH – ''Methanocaldococcus jannaschii''<br />
3prl – BhGAPDH – ''Bacillus halodurans''<br />
===NAD-dependent GAPDH with cofactor NAD===
1vsv – CpGAPDH + NAD<br />
1gpd – GAPDH + NAD – American lobster<br />
3gpd, 1znq, 1u8f - GAPDH + NAD – human<br />
2vyn, 2vyv - GAPDH + NAD - rat<br />
1gd1, 3cmc – GsGAPDH + NAD – ''Geobacillus stearothermophilus''<br />
1dbv, 3dbv - GsGAPDH (mutant) + NAD<br />
1hdg - GAPDH + NAD – ''Thermotoga maritima''<br />
1gyp, 1a7k - GAPDH + NAD – ''Leishmania mexicana''<br />
1gyq - LmGAPDH + benzyl-NAD<br />
1cer, 2g82 - GAPDH + NAD – ''Thermus aquaticus''<br />
1gad, 1dc6 - EcGAPDH + NAD<br />
1gae - EcGAPDH (mutant) + NAD<br />
2ep7 – GAPDH + NAD – ''Aquifex aeolicus''<br />
1nbo - sGAPDH + NAD<br />
1j0x - GAPDH + NAD – rabbit<br />
2b4r, 1ywg - PfGAPDH + NAD – ''Plasmodium falciparum''<br />
2b4t - PfGAPDH (mutant) + NAD<br />
2czc - GAPDH + NAD – ''Pyrococcus horikoshii''<br />
2i5p - GAPDH + NAD – ''Kluyveromyces marxianus''<br />
3gnq - GAPDH + NAD – ''Burkholderia pseudomallei''<br />
3hja - GAPDH + NAD – ''Borrelia burgdorferi''<br />
3e5r - RiGAPDH + NAD<br />
2x0n – GAPDH + NAD – ''Trypanosoma brucei'' – Laue<br />
3k2b -  GAPDH + NAD – ''Arabidopsis thaliana''<br />
3hq4, 3k9q, 3ksd, 3lc1 - SaGAPDH (mutant) + NAD<br />
3lvf - SaGAPDH + NAD<br />
3pfw - hGAPDH + NAD – human<br />
3sth - GAPDH + NAD – ''Toxoplasma gondii''<br />
3pym - GAPDH + NAD – yeast<br />
===NAD-dependent GAPDH ternary complexes containing glyceraldehyde-3-phosphate (G3P)===
3cif - CpGAPDH (mutant) + NAD + G3P<br />
3ksz, 3l4s - SaGAPDH (mutant) + NAD + G3P<br />
===Other NAD-dependent GAPDH ternary complexes===
3dmt, 3ids - TcGAPDH  + NAD + inhibitor<br />
3h9e - hGAPDH + NAD + phosphate<br />
3k73, 3l6o - SaGAPDH + NAD + phosphate<br />
1uxt - TtGAPDH (mutant) + NAD + G1P<br />
3b1j, 3b1k - GAPDH + NAD + CP12 – ''Synechococcus elongatus''<br />
===NADP-dependent GAPDH with cofactor NADP===
2dbv, 4dbv - GsGAPDH (mutant) + NADP<br />
2yyy - MjGAPDH + NADP<br />
2euh - SmGAPDH + NADP<br />
2id2 - SmGAPDH (mutant) + NADP<br />
1cf2 - GAPDH + NADP – ''Methanothermus fervidus''<br />
1jn0, 1rm4, 2pkq, 2pkr - sGAPDH  + NADP<br />
1rm3, 1rm5 - sGAPDH (mutant) + NADP<br />
1ky8 - TtGAPDH + NADP – ''Thermoproteus tenax''<br />
3rhh - BhGAPDH + NADP<br />
===NADP-dependent GAPDH ternary complexes containing glyceraldehyde-3-phosphate (G3P)===
1qi1 - SmGAPDH + NADP + G3P<br />
2esd, 2qe0 - SmGAPDH (mutant) + NADP + G3P<br />
3lc2 – SaGAPDH-thioacyl + G3P<br />
1uxu - TtGAPDH (mutant) + NADP + AMP + G3P<br />
===Other NADP-dependent GAPDH ternary complexes===
1k3t - TcGAPDH  + coumarin derivative – ''Trypanosoma cruzi''<br />
1uxv - TtGAPDH + NADP + AMP<br />
1uxp - TtGAPDH (mutant) + NADP + ADP<br />
1uxq - TtGAPDH (mutant) + NADP + G1P<br />
1uxr - TtGAPDH (mutant) + NADP + F6P<br />


==References==
==References==
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6) <ref group="xtra">PMID: 22851451</ref><references group="xtra"/>
6) <ref group="xtra">PMID: 22851451</ref><references group="xtra"/>
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Nathan Line, David Canner, Andrew Swart, Alice Harmon, Michal Harel, Alexander Berchansky
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