Aldehyde dehydrogenase

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* '''ALDH class 2''' is mitochondrial. <br />
* '''ALDH class 2''' is mitochondrial. <br />
* '''ALDH class 3''' is found in tumors, stomach and cornea. '''ALDH3A1''' is soluble and has substrate specificity to bulky aromatic aldehydes. '''ALDH3A2''' is a fatty ALDH (FALDH). FALDH was found to have an additional gatekeeper helix at the substrate funnel entrance that is shaping the enzymes substrate specificity. <ref>Keller, Markus A.; Zander, Ulrich; Fuchs, Julian E.; Kreutz, Christoph; Watschinger, Katrin et al. (2014). A gatekeeper helix determines the substrate specificity of Sjögren–Larsson Syndrome enzyme fatty aldehyde dehydrogenase. Nature Communications vol. 5.</ref><br />
* '''ALDH class 3''' is found in tumors, stomach and cornea. '''ALDH3A1''' is soluble and has substrate specificity to bulky aromatic aldehydes. '''ALDH3A2''' is a fatty ALDH (FALDH). FALDH was found to have an additional gatekeeper helix at the substrate funnel entrance that is shaping the enzymes substrate specificity. <ref>Keller, Markus A.; Zander, Ulrich; Fuchs, Julian E.; Kreutz, Christoph; Watschinger, Katrin et al. (2014). A gatekeeper helix determines the substrate specificity of Sjögren–Larsson Syndrome enzyme fatty aldehyde dehydrogenase. Nature Communications vol. 5.</ref><br />
-
* '''ALDH family 7 member A1''' is known as '''antiquitin''' and functions in the detoxification of aldehydes.
+
* '''ALDH family 7 member A1''' is known as '''antiquitin''' and functions in the detoxification of aldehydes. <br />
 +
* '''Glyceraldehyde-3-phophate (G3P)-ALDH''' is called GAPDH. GADPH catalyzes the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate in the presence of inorganic phosphate (Pi) and NAD. A cysteine-thiol at the active site of GAPDH plays a role I catalysis. The aldehyde of G3P reacts with the cysteine-thiol to form a carboxylic acid in a high energy thioester form. The thioester is attacked by the inorganic phosphate and forms the acyl phosphate. GAPDH is part of the glycolysis pathway. GAPDH contains NAD-dependent and NADPH-dependent enzymes.
== 3D Structures of Aldehyde dehydrogenase ==
== 3D Structures of Aldehyde dehydrogenase ==
Line 146: Line 147:
**[[3lns]] - Benzaldehyde-PpALDH3 + NADP + benzoate<BR />
**[[3lns]] - Benzaldehyde-PpALDH3 + NADP + benzoate<BR />
**[[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
**[[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
-
**[[2vro]] – BxALDH + NADP + alcohol
+
**[[2vro]] – BxALDH + NADP + alcohol <br />
 +
 
 +
*NAD-dependent glyceraldehydes-3-phosphate dehydrogenase
 +
 
 +
**[[1vsu]] – CpGAPDH – ''Cryptosporidium parvum''<br />
 +
**[[1ywg]] – PfGAPDH – ''Plasmodium falciparum''<br />
 +
**[[3cmc]] - GAPDH – ''Bacillus stearothermophilus''<br />
 +
**[[2ep7]] – GAPDH – ''Aquifex aeolicus''<br />
 +
**[[2i5p]] – GAPDH – ''Kluyveromyces marxianus''<br />
 +
**[[1obf]] – GAPDH – ''Achromobacter xylosoxidans''<br />
 +
**[[1b7g]] – GAPDH – ''Sulfolobus solfataricus''<br />
 +
**[[2gd1]] – GsGAPDH – ''Geobacillus stearothermophilus''<br />
 +
**[[3e6a]] – OsGAPDH – ''Oryza sativa''<br />
 +
**[[4gpd]], [[1gpd]], [[1crw]] – GAPDH – lobster<br />
 +
**[[3l6o]], [[3lc7]] – SaGAPDH<br />
 +
**[[1dc3]], [[1dc5]], [[1s7c]] – EcGAPDH - ''Escherichia coli''<br />
 +
 
 +
*''GAPDH binary complex''
 +
 
 +
**[[1k3t]] - TcGAPDH + inhibitor<br />
 +
**[[3hja]] - GAPDH + NAD – ''Borellia burgdorferi''<br />
 +
**[[1vsv]], [[3cps]] - CpGAPDH + NAD<br />
 +
**[[2vyn]], [[2vyv]] - rGAPDH residues 102-432 + EcGAPDH + NAD<br />
 +
**[[2b4r]], [[2b4t]] – PfGAPDH (mutant) + NAD<br />
 +
**[[1j0x]] – GAPDH + NAD – rabbit<br />
 +
**[[1ihx]] – PvGAPDH + NAD <br />
 +
**[[1dss]], [[1szj]] - PvGAPDH NAD-binding and catalytic domains+ NAD<br />
 +
**[[1ihy]] – PvGAPDH + ADP-ribose<br />
 +
**[[1gyq]], [[1gyp]] - LmGAPDH + NAD derivative – ''Leishmania mexicana''<br />
 +
**[[1i32]], [[1i33]] – LmGAPDH + inhibitor<br />
 +
**[[1a7k]] – LmGAPDH + NAD<br />
 +
**[[1cer]], [[2g82]] - GAPDH + NAD – ''Thermus aquaticus''<br />
 +
**[[1gd1]] - GsGAPDH + NAD<br />
 +
**[[1npt]], [[1nq5]], [[1dbv]], [[2dbv]], [[3dbv]], [[4dbv]] - GsGAPDH (mutant) + NAD<br />
 +
**[[3e5r]] – OsGAPDH + NAD <br />
 +
**[[3k73]], [[3lvf]] – SaGAPDH + NAD<br />
 +
**[[3lc2]] - SaGAPDH + G3P<br />
 +
**[[3k9q]], [[3ksd]], [[3lc1]], [[3hq4]] - SaGAPDH (mutant) + NAD<br />
 +
**[[3gpd]], [[2u8f]], [[1znq]] – hGAPDH + NAD<br />
 +
**[[1gad]], [[1dc6]] - EcGAPDH + NAD<br />
 +
**[[1gae]] - EcGAPDH (mutant) + NAD<br />
 +
**[[1dc4]] – EcGAPDH + G3P<br />
 +
 
 +
*''GAPDH ternary complex''
 +
 
 +
**[[3id5]], [[3dmt]], [[1ml3]] – TcGAPDH + NAD + inhibitor <br />
 +
**[[1qxs]] - TcGAPDH + NAD + G3P analog<br />
 +
**[[3cif]] - CpGAPDH + NAD + G3P<br />
 +
**[[1nqa]], [[1nqo]] - GsGAPDH (mutant) + NAD + G3P<br />
 +
**[[3ksz]], [[3kv3]], [[3l4s]] - SaGAPDH (mutant) + NAD + G3P<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 <br />
 +
**[[1uxv]] - TtGAPDH + NADP + AMP<br />
 +
**[[1uxp]] - TtGAPDH (mutant) + NADP + ADP<br />
 +
**[[1uxq]] - TtGAPDH (mutant) + NADP + G1P<br />
 +
**[[1uxr]] - TtGAPDH (mutant) + NADP + F6P
*Uncharacterized ALDH
*Uncharacterized ALDH

Revision as of 06:47, 12 April 2015

Image:1nzx.png
Crystal Structure of Aldehyde dehydrogenase, 1nzx

Template:STRUCTURE 1o9j











Aldehyde dehydrogenase (ALDH) converts aldehydes to carboxylic acids while reducing NAD+ to NADH. In mammals there are 3 classes of ALDH and each contain constitutive and inducible forms.

  • ALDH class 1 is cytosolic.
  • ALDH class 2 is mitochondrial.
  • ALDH class 3 is found in tumors, stomach and cornea. ALDH3A1 is soluble and has substrate specificity to bulky aromatic aldehydes. ALDH3A2 is a fatty ALDH (FALDH). FALDH was found to have an additional gatekeeper helix at the substrate funnel entrance that is shaping the enzymes substrate specificity. [1]
  • ALDH family 7 member A1 is known as antiquitin and functions in the detoxification of aldehydes.
  • Glyceraldehyde-3-phophate (G3P)-ALDH is called GAPDH. GADPH catalyzes the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate in the presence of inorganic phosphate (Pi) and NAD. A cysteine-thiol at the active site of GAPDH plays a role I catalysis. The aldehyde of G3P reacts with the cysteine-thiol to form a carboxylic acid in a high energy thioester form. The thioester is attacked by the inorganic phosphate and forms the acyl phosphate. GAPDH is part of the glycolysis pathway. GAPDH contains NAD-dependent and NADPH-dependent enzymes.

3D Structures of Aldehyde dehydrogenase

Updated on 12-April-2015

References

  1. Keller, Markus A.; Zander, Ulrich; Fuchs, Julian E.; Kreutz, Christoph; Watschinger, Katrin et al. (2014). A gatekeeper helix determines the substrate specificity of Sjögren–Larsson Syndrome enzyme fatty aldehyde dehydrogenase. Nature Communications vol. 5.

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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