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Aldehyde dehydrogenase: Difference between revisions

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<StructureSection load='1o9j' size='350' side='right' scene='44/447036/Cv/2' caption='Aldehyde hydrogenase class 1 tetramer complex with NAD, dithiothreitol and dimercaptobutane-diol, [[1o9j]]'>
<StructureSection load='' size='450' side='right' scene='44/447036/Cv/2' caption='Aldehyde hydrogenase class 1 tetramer complex with NAD, dithiothreitol and dimercaptobutane-diol, [[1o9j]]'>


== Function ==
== Function ==
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'''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.<br />
'''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.<br />
* '''ALDH class 1''' is cytosolic.<br />
* '''ALDH class 1''' is cytosolic.<br />
* '''RALDH class 1A 1''' is retinal dehydrogenase which converts retinalaldehyde to retinoic acid.<br />
* '''RALDH class 1A 2''' is retinal dehydrogenase which converts retinal to retinoate.<br />
* '''RALDH class 1A 3''' is retinal dehydrogenase which funcrions in detoxification of aldehydes.<br />
* '''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. <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 ==
Line 20: Line 29:
== Structural highlights ==
== Structural highlights ==


A cysteine-thiol at the active site of GAPDH plays a role in catalysis. <scene name='44/447036/Cv/3'>Active site</scene>.
A cysteine-thiol at the active site of GAPDH plays a role in catalysis.  
</StructureSection>
*<scene name='44/447036/Cv/9'>Active site</scene>. Water molecules shown as red spheres.
== 3D Structures of Aldehyde dehydrogenase ==
*<scene name='44/447036/Cv/10'>Dithiothreitol binding</scene>.
 
*<scene name='44/447036/Cv/11'>Dimercaptobutane-diol binding</scene>.
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|


*ALDH class 1
== 3D Structures of aldehyde dehydrogenase ==
[[Aldehyde dehydrogenase 3D structures]]


**[[3fx4]] – ALDH1 + NADP + inhibitor – pig<BR />
</StructureSection>
**[[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 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
 
*ALDH class 3
 
**[[1ad3]] – rALDH3<br />
**[[3sza]] - hALDH3A1<br />
**[[3szb]], [[4l1o]], [[4l2o]] – hALDH3A1 + inhibitor<br />
**[[4h80]] - hALDH3A1 (mutant) + inhibitor<br />
**[[4qgk]] – hALDH3A2 + ligand<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 />
**[[3llg]], [[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]], [[4ps9]] – BcALDH – ''Bacillus cereus''<br />
**[[4qet]] – BcALDH (mutant)<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 />
**[[4pt0]] – BcALDH + NAD<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 />
 
*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 />
**[[3ifg]], [[3ifh]] - 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 /> 
**[[3lv1]] – Benzaldehyde-PpALDH3 + NADP – ''Pseudomonas putida''<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]] - ALDH + NADP – ''Burkholderia multivorans''<br />
**[[5j6b]] - BtALDH + NADP <br />
**[[4pt3]] – BcALDH + NADP<br />
 
*NADP-dependent  ALDH ternary complexes
 
**[[3lns]] - Benzaldehyde-PpALDH3 + NADP + benzoate<BR />
**[[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
**[[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
 
**[[3k9d]] – ALDH – ''Listeria monocytogenes''<br />
**[[4dng]] – ALDH – ''Bacillus subtilis''<br />
**[[3my7]] – ALDH – ''Vibrio parahaemolyticus''<br />
 
*Antiquitin
 
**[[2jg7]] – Antiquitin – ''Acanthopagrus schlegeli''


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


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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman
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