Glyceraldehyde-3-Phosphate Dehydrogenase: Difference between revisions

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{{STRUCTURE_3gpd|  PDB=3gpd | SIZE=400| SCENE= |right|CAPTION=Human glyceraldehyde-3-phosphate dehydrogenase complex with NAD and sulfate, [[3gpd]] }}
<StructureSection load='3gpd' size='340' side='right' caption='Human glyceraldehyde-3-phosphate dehydrogenase complex with NAD and sulfate, [[3gpd]]' scene=''>
 
== Function ==
== Function ==


'''Glyceraldehyde-3-phosphate dehydrogenase''' (GAPDH) is a very important enzyme in the production of energy and in photosynthesis.  In the production of energy this enzyme catalyzes the sixth step in the process of breaking down glucose, also known as glycolysis which occurs in organisms of all phyla. The sixth step consists of of the oxidation of GAP by '''NAD''' and an inorganic phosphate to yield 1,3 bisphosphoglycerate.  In photosynthesis, which is carried out by plants and algae, this enzyme uses '''NADPH''' in the reverse reaction in a step in the Calvin Cycle, which fixes gaseous CO<sub>2</sub> into carbohydrate. Though these are its main functions, GAPDH has been shown to perform other functions including transcription activation, initiation of apoptosis, and ER to Golgi apparatus vesicle transportation <ref>PMID: 22851451</ref>.  However, this page will focus on GAPDH’s role in glycolysis. See [[2pkq]] for the plant Calvin Cycle enzyme. See [[Glycolysis Enzymes]].
'''Glyceraldehyde-3-phosphate dehydrogenase''' (GAPDH) is a very important enzyme in the production of energy and in photosynthesis.  In the production of energy this enzyme catalyzes the sixth step in the process of breaking down glucose, also known as [[glycolysis]] which occurs in organisms of all phyla. The sixth step consists of of the oxidation of GAP by [[NAD]] and an inorganic phosphate to yield 1,3 bisphosphoglycerate.  In photosynthesis, which is carried out by plants and algae, this enzyme uses '''NADPH''' in the reverse reaction in a step in the [[Calvin cycle]], which fixes gaseous CO<sub>2</sub> into carbohydrate. Though these are its main functions, GAPDH has been shown to perform other functions including transcription activation, initiation of apoptosis, and ER to Golgi apparatus vesicle transportation <ref>PMID: 22851451</ref>.  However, this page will focus on GAPDH’s role in glycolysis. See [[2pkq]] for the plant Calvin Cycle enzyme. See [[Glycolysis Enzymes]] and [[Carbon Fixation]].


== Structure ==
== Structure ==


GAPDH most commonly exists as what looks to be a dimer.  Interesting though, the two monomers of the enzyme are not exactly the same.  While one side consists only of parallel and antiparallel beta-sheets, the other monomer is made up of both <scene name='Nathan_Line_sandbox_3/Secondary_structure/1'>beta-sheets and alpha helixes</scene>. Though each monomer does not have to exact same sequence, each does contain replicate active sites and function.  This is consistent with the following SCOP information:
GAPDH most commonly exists as what looks to be a dimer.  Interesting though, the two monomers of the enzyme are not exactly the same.  While one side consists only of parallel and antiparallel beta-sheets, the other monomer is made up of both <scene name='Nathan_Line_sandbox_3/Secondary_structure/1'>beta-sheets and alpha helixes</scene>. Though each monomer does not have to exact same sequence, each does contain replicate active sites and function.  This is consistent with the following SCOP information:


Class: Alpha and beta proteins (a/b)
Class: Alpha and beta proteins (a/b)
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==3D structures of glyceraldehyde-3-phosphate dehydrogenase==
==3D structures of glyceraldehyde-3-phosphate dehydrogenase==
[[Glyceraldehyde-3-phosphate dehydrogenase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*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==


1) Voet, D, Voet, J, & Pratt, C. (2008). Fundamentals of biochemistry, third edition. Hoboken, NJ: Wiley & Sons, Inc.
1) Voet, D, Voet, J, & Pratt, C. (2008)
 
2)Family: Glyceraldehyde-3-phosphate dehydrogenase-like, N-terminal domain. Retrieved from: http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.d.c.b.d.html
2)Family: Glyceraldehyde-3-phosphate dehydrogenase-like, N-terminal domain. Retrieved from: http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.d.c.b.d.html


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Nathan Line, David Canner, Andrew Swart, Alice Harmon, Michal Harel, Alexander Berchansky