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* '''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. <br />
* '''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. 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.
* '''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. 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 and [[Calvin cycle]]. GAPDH contains NAD-dependent and NADPH-dependent enzymes. For the complex of ALDH and nitroglycerine see [[NitroDur]].
* '''Indole-3-acetaldehyde dehydrogenase''' catalyzes the formation of indole-3-acetic acid from indole-3-acetaldehyde<ref>PMID:29293681</ref>.<br />
 
 
See also:
*[[Pyrroline-5-carboxylate dehydrogenase]]
*[[Succinate-semialdehyde dehydrogenase]]


== Disease ==
== Disease ==


ALDH inhibition is associate with Parkinson disease. Inhibitors can include pesticides.  Mitochondrial ALDH2 deficiency causes accumulation of acetaldehyde in the blood following alcohol consumption resulting in the syndrome known as Alcohol flush syndrome.   
ALDH inhibition is associate with Parkinson disease. Inhibitors can include pesticides.  Mitochondrial ALDH2 deficiency causes accumulation of acetaldehyde in the blood following alcohol consumption resulting in the syndrome known as Alcohol flush syndrome.   


== Relevance ==
== Relevance ==
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*<scene name='44/447036/Cv/10'>Dithiothreitol binding</scene>.
*<scene name='44/447036/Cv/10'>Dithiothreitol binding</scene>.
*<scene name='44/447036/Cv/11'>Dimercaptobutane-diol binding</scene>.
*<scene name='44/447036/Cv/11'>Dimercaptobutane-diol binding</scene>.
</StructureSection>
== 3D Structures of Aldehyde dehydrogenase ==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
== 3D Structures of aldehyde dehydrogenase ==
{{#tree:id=OrganizedByTopic|openlevels=0|
[[Aldehyde dehydrogenase 3D structures]]


*ALDH class 1
</StructureSection>
 
**[[3fx4]] – ALDH1 + NADP + inhibitor – pig<BR />
**[[1bxs]] – sALDH1 + NAD - sheep<br />
**[[5abm]] - sALDH1 + NAD derivative<br />
**[[5ac0]] - sALDH1 + NAD + duocarmycin analog<br />
**[[5ac1]], [[5ac2]] - sALDH1 + duocarmycin analog<br />
**[[1o9j]] – ALDH1 + NAD – Elephant shrew<br />
**[[3rhj]], [[3rhl]], [[3rho]], [[3rhp]], [[3rhq]], [[3rhr]] – rALDH1 C- terminal (mutant) + NADP – rat<br />
**[[3rhm]] - rALDH1 C- terminal<br />
**[[1hso]] – hALDH1 α subunit + Zn + NAD - human<br />
**[[4wj9]] - hALDH1 (mutant) <br />
**[[4wpn]] - hALDH1 + inhibitor<br />
**[[4wp7]] - hALDH1 (mutant) + inhibitor<br />
**[[4wb9]] - hALDH1 + NAD derivative <br />
**[[4x4l]] - hALDH1 + NAD derivative + inhibitor<br />
**[[1ht0]] – hALDH1 γ subunit (mutant) + Zn + NAD
 
*ALDH class 1 A (retinal dehydrogenase)
 
**[[5l2m]], [[5l2n]], [[5l2o]] – hRALDH1 + inhibitor<br />
**[[5tei]] – hRALDH1 + NAD + inhibitor<br />
**[[6alj]], [[6b5g]], [[6b5h]], [[6b5i]] – hRALDH2 + NAD + inhibitor<br />
**[[5fhz]] – hRALDH3 + NAD + retinol<br />
 
*ALDH class 2
 
**[[3n80]], [[1o05]], [[4kwf]] – hALDH2 residues 18-517<BR />
**[[3n81]], [[2onn]], [[2ono]], [[1zum]] – hALDH2 residues 18-517 (mutant) <BR />
**[[1ag8]] – bALDH NAD binding domain - bovine
 
*ALDH2 binary complex
 
**[[3inj]], [[3inl]], [[4kwg]] - hALDH2 residues 18-517 + agonist<BR />
**[[2vle]] - hALDH2 residues 24-517 + daidzin<BR />
**[[1nzx]], [[1nzz]], [[1o00]], [[1o02]], [[1cw3]], [[4x2q]] - hALDH2 residues 18-517 + NAD<BR />
**[[3n82]], [[3n83]], [[2onm]], [[2onp]], [[1nzw]], [[1o04]] – hALDH2 residues 18-517 (mutant) + NADH<BR />
**[[3sz9]] - hALDH2 residues 18-517 + inhibitor<br />
**[[1a4z]] – bALDH2 NAD-binding domain + NAD<BR />
**[[1bi9]] – rALDH2 + NAD<br />
**[[4pxl]] – ALDH2 + NAD - maize<br />
 
*ALDH2 ternary complex
 
**[[1o01]] - hALDH2 residues 18-517 + NADH + aldehyde<br />
**[[4fqf]] - hALDH2 residues 18-517 + NAD + NO2<br />
**[[4fr8]] - hALDH2 residues 18-517 (mutant) + NAD + ADP + nitroglycerin<br />
**[[5l13]] – hALDH2 + inhibitor<br />
 
*ALDH class 3
 
**[[1ad3]] – rALDH3<br />
**[[3sza]] - hALDH3A1<br />
**[[3szb]], [[4l1o]], [[4l2o]] – hALDH3A1 + inhibitor<br />
**[[4h80]] - hALDH3A1 (mutant) + inhibitor<br />
**[[4qgk]] – hALDH3A2 + ligand<br />
**[[5myp]] – TbALDH – ''Trypanosoma brucei''<br />
**[[5nno]] – TbALDH + NAD + inhibitor <br />
 
*NAD-dependent  ALDH
 
**[[2w8n]], [[2w8o]], [[2w8r]] – Succinate–semi-hALDH family 5<BR />
**[[2w8p]] - Succinate–semi-hALDH family 5 (mutant) <BR />
**[[3r31]] – Betaine-ALDH – ''Agrobacterium tumefaciens''<BR />
**[[4mpb]], [[4nu9]], [[4q92]], [[4qto]] - Betaine-SaALDH  – ''Staphylococcus aureus''<BR />
**[[4qje]] - Betaine-SaALDH (mutant)<br />
**[[4zxu]], [[4zwl]] - Betaine-SaALDH (mutant) + NAD<br />
**[[4cbb]] - Betaine-PaALDH - ''Pseudomonas aeruginosa''<br />
**[[1a4s]] - Betaine-cALDH - cod<BR />
**[[3vos]], [[3tz6]], [[3vos]] – Aspartate-semi-MtALDH<BR /> 
**[[2cq8]] - Formyltetrahydrofolate-hALDH PP-binding domain - NMR<BR />
**[[2nac]] – Formate-PsALDH<BR />
**[[3i44]] – ALDH – ''Bartonella henselae''<BR />
**[[3ek1]] – ALDH – ''Brucella melitensis''<br />
**[[3ros]] – ALDH – ''Lactobacillus acidophilus''<br />
**[[3r64]] – ALDH – ''Corynebacterium glutamicum''<br />
**[[3rhe]] – Benzaldehyde-ALDH – ''Legionella pneumophila''<br />
**[[3u4j]], [[4i3t]] – SmALDH – ''Sinorhizobium meliloti''<br />
**[[5dru]] - CpALDH – ''Clostridium phytofermentans''<br />
**[[4qf6]], [[5gt6]] – BcALDH – ''Bacillus cereus''<br />
**[[4qet]] – BcALDH (mutant)<br />
**[[5uju]] - BmALDH – ''Burkholderia multivorans''<br />
 
*NAD-dependent  ALDH binary complexes
 
**[[2w8q]] - Succinate–semi-hALDH family 5 + succinic acid<BR />
**[[4mpy]], [[4nea]] - Betaine-SaALDH + NAD<BR />
**[[4qn2]], [[5ez4]], [[5eyu]], [[5dib]] - Betaine-SaALDH (mutant) + NAD<br />
**[[1bpw]] - Betaine-cALDH + NAD<BR />
**[[2j6l]] – Aminoadipate-semi-hALDH family 7 + NAD<BR />
**[[2cfi]] - Formyltetrahydrofolate-hALDH hydrolase domain + formyltetrahydropterin<BR />
**[[2nad]] - Formate-PaALDH + NAD <BR />
**[[3l4p]], [[1sij]] – ALDH + AsO3 – ''Desulfovibrio gigas''<br />
**[[4a0m]], [[4v37]] – spALDH + NAD – spinach<br />
**[[5a2d]], [[4v3f]] – spALDH + choline<br />
**[[3iwk]] – amino-ALDH + NAD – pea<br />
**[[3ju8]] - Succinylglutamic–semi-PaALDH + NAD <br />
**[[4caz]] - Betaine-PaALDH + NAD derivative<br />
**[[4c3s]] - CpALDH + NAD <br />
**[[5dbv]] - CpALDH + CoA <br />
**[[4i3u]] – SmALDH + phosphonoacetaldehyde<br />
**[[5gtk]] – BcALDH + NAD<br />
**[[5jfl]] – RpALDH + NAD – ''Rhodopseudomonas palustris''<br />
**[[5jfn]] – RpALDH + CoA <br />
 
*NAD-dependent  ALDH ternary complexes
 
**[[2gsd]] – Formate-ALDH + NAD + azide – ''Moraxella''<BR />
**[[1nvm]] – Acetaldehyde-PsALDH + 4-hydroxy-oxovalerate aldolase + NAD<BR />
**[[1llu]] - PaALDH + NAD + alcohol<br />
**[[4i3v]], [[4i3w]] – SmALDH + aldehyde derivative + NAD<br />
**[[4i3x]] – SmALDH + phosphonoacete + NAD<br />
**[[5jfm]] – RpALDH + CoA + propionyl-CoA<br />
 
*NADP-dependent  ALDH
 
**[[3k2w]] - Betaine-ALDH – ''Pseudoalteromonas atlantica''<BR />
**[[2hg2]], [[2opx]] – Lactaldehyde-EcALDH <BR />
**[[2o2p]] – Formyltetrahydrofolate-rALDH C-terminal<br />
**[[2y51]], [[2y52]], [[2y53]], [[2y5d]] – BxALDH (mutant) – ''Burkholderia xenovorans''<br />
**[[4v6h]] - Succinate–semi-ALDH – ''Burkholderia pseudomallei''<br />
**[[3rh9]] - Succinate–semi-ALDH – ''Marinobacter aquaeolei''<br />
**[[3uw3]] - aspartate–semi-BtALDH – ''Burkholderia thailandensis''<br />
**[[3v4c]] - SmALDH<br />
**[[4gac]] – ALDH – mouse<br />
**[[5eeb]] - PfALDH – ''Pyrobaculum ferrireducens''<br />
 
*NADP-dependent  ALDH binary complexes
 
**[[2wox]], [[2wme]], [[2xdr]], [[3zqa]] - Betaine-PaALDH + NADP<BR /> 
**[[2ilu]] - Lactaldehyde-EcALDH + NADP<BR />
**[[3rhd]] - Lactaldehyde-MjALDH + NADP - ''Methanocaldococcus jannaschii''<br />
**[[2o2q]], [[2o2r]] - Formyltetrahydrofolate-rALDH C-terminal + NADP<BR />
**[[3b4w]] - MtALDH + NADP – ''Mycobacterium tuberculosis''<BR />
**[[1eyy]], [[1ez0]] – ALDH + NADP – ''Vibrio harveyi''<br />
**[[3jz4]] - Succinate–semi-EcALDH + NADP<br />
**[[3hsk]] - aspartate–semi-ALDH + NADP – ''Candida albicans''<br />
**[[4h73]], [[4nmj]], [[4nmk]], [[5f2c]], [[5exf]], [[5euy]], [[5ekc]], [[5ek6]] - PfALDH + NADP <br />
**[[5kf0]] - ALDH + NADP – ''Burkholderia vietnamiensis''<br />
**[[5jry]] - BmALDH + NADP <br />
**[[5j6b]] - BtALDH + NADP <br />
**[[5gtl]] – BcALDH + NADP<br />
 
*NADP-dependent  ALDH ternary complexes
 
**[[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
**[[2vro]] – BxALDH + NADP + alcohol <br />
 
*Indole-3-ALDH
 
**[[5iuu]] – PsIALDH – ''Pseudomonas syringae''<br />
**[[5iuv]] – PsIALDH + NAD<br />
**[[5iuw]] – PsIALDH + NAD + indole acetate<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
 
**[[3k9d]] – ALDH – ''Listeria monocytogenes''<br />
**[[4dng]] – ALDH – ''Bacillus subtilis''<br />
**[[3my7]] – ALDH – ''Vibrio parahaemolyticus''<br />
**[[4qyj]] - PpALDH<br />
**[[5mz5]] – PhpALDH 21 – ''Physcomitrella patens''<br />
**[[5mz8]] – PhpALDH 21 + succinate<br />
**[[5n5s]] – PhpALDH 21 + NADP<br />
 
*Antiquitin
 
**[[2jg7]] – Antiquitin – ''Acanthopagrus schlegeli''


}}
==References==
==References==
{{reflist}}
{{reflist}}
<references/>


[[Category:Topic Page]]
[[Category:Topic Page]]

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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