Aldehyde dehydrogenase: Difference between revisions

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[[Image:1nzx.png|left|200px|thumb|Crystal Structure of Aldehyde dehydrogenase, [[1nzx]]]]
<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]]'>
{{STRUCTURE_1o9j|  PDB=1o9j  | SIZE=400| SCENE=|right|CAPTION=Aldehyde hydrogenase class 1 tetramer complex with NAD, dithiothreitol and dimercaptobutane-diol , [[1o9j]] }}


== Function ==


'''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 />
* '''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 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 />
* '''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 ==


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 ==


Buildup of toxic aldehydes causes cell damage and cardiac diseases.


== Structural highlights ==


A cysteine-thiol at the active site of GAPDH plays a role in catalysis.
*<scene name='44/447036/Cv/9'>Active site</scene>. Water molecules shown as red spheres.
*<scene name='44/447036/Cv/10'>Dithiothreitol binding</scene>.
*<scene name='44/447036/Cv/11'>Dimercaptobutane-diol binding</scene>.


== 3D Structures of aldehyde dehydrogenase ==
[[Aldehyde dehydrogenase 3D structures]]


</StructureSection>


 
==References==
 
{{reflist}}
 
<references/>
 
 
 
 
 
'''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.  Class 1 is cytosolic; class 2 mitochondrial; class 3 found in tumors, stomach and cornea.  ALDH family 7 member A1 is known as '''antiquitin''' and functions in the detoxification of aldehydes.
 
== 3D Structures of Aldehyde dehydrogenase ==
 
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
 
===ALDH class 1===
 
[[3fx4]] – ALDH1 + NADP + inhibitor – pig<BR />
[[1bxs]] – ALDH1 - sheep<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<br />
[[1ht0]] – hALDH1 γ subunit (mutant) + Zn + NAD
 
===ALDH class 2===
 
[[3n80]], [[1o05]] – hALDH2 residues 18-517- human<BR />
[[3n81]], [[2onn]], [[2ono]], [[1zum]] – hALDH2 residues 18-517 (mutant) <BR />
[[1ag8]] – bALDH NAD binding domain - bovine
 
''Binary complex''
 
[[3inj]], [[3inl]] - hALDH2 residues 18-517 + agonist<BR />
[[2vle]] - hALDH2 residues 24-517 + daidzin<BR />
[[1nzx]], [[1nzz]], [[1o00]], [[1o02]], [[1cw3]] - 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 />
 
''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]] – rALDH<br />
[[3sza]] - hALDH<br />
[[3szb]] – hALDH + inhibitor<br />
[[4h80]] - hALDH (mutant) + 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 />
[[3ed6]], [[4mpb]], [[4nu9]] - Betaine-SaALDH  – ''Staphylococcus aureus''<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''
 
''Binary complexes''
 
[[2w8q]] - Succinate–semi-hALDH family 5 + succinic acid<BR />
[[3fg0]], [[4mpy]], [[4nea]] - Betaine-SaALDH + NAD<BR />
[[4ni4]] - 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-PsALDH + NAD – ''Pseudomonas''<BR />
[[1bi9]] – Retinal-rALDH2 + NAD<BR />
[[3l4p]], [[1sij]] – ALDH + AsO3 – ''Desulfovibrio gigas''<br />
[[4a0m]] – spALDH + NAD – spinach<br />
[[3iwk]] – amino-ALDH + NAD – pea<br />
[[3ju8]] - Succinylglutamic–semi-PaALDH + NAD – ''Pseudomonas aeruginosa''<br />
[[4c3s]] - ALDH + NAD – ''Clostridium phytofermentans''<br />
[[4i3u]] – SmALDH + phosphonoacetaldehyde<br />
 
''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-ALDH – ''Burkholderia thailandensis''<br />
[[3v4c]] - SmALDH
 
''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]] - ALDH + NADP – ''Pyrobaculum''<br />
 
''Ternary complexes''
 
[[3lns]] - Benzaldehyde-PpALDH3 + NADP + benzoate<BR />
[[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
[[2vro]] – BxALDH + NADP + alcohol
 
 
[[3k9d]] – ALDH – ''Listeria monocytogenes''
 
===Antiquitin===
 
[[2jg7]] – Antiquitin – Acanthopagrus schlegeli
 
[[3my7]] – ALDH – ''Vibrio parahaemolyticus''
 
 
 
 
 
 
 
 
 
 
 
 


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

Latest revision as of 11:44, 22 May 2024


Function

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.
  • RALDH class 1A 1 is retinal dehydrogenase which converts retinalaldehyde to retinoic acid.
  • RALDH class 1A 2 is retinal dehydrogenase which converts retinal to retinoate.
  • RALDH class 1A 3 is retinal dehydrogenase which funcrions in detoxification of aldehydes.
  • 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. 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[2].


See also:

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.

Relevance

Buildup of toxic aldehydes causes cell damage and cardiac diseases.

Structural highlights

A cysteine-thiol at the active site of GAPDH plays a role in catalysis.

  • . Water molecules shown as red spheres.
  • .
  • .

3D Structures of aldehyde dehydrogenase

Aldehyde dehydrogenase 3D structures


Aldehyde hydrogenase class 1 tetramer complex with NAD, dithiothreitol and dimercaptobutane-diol, 1o9j

Drag the structure with the mouse to rotate

ReferencesReferences

  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.
  2. ↑ McClerklin SA, Lee SG, Harper CP, Nwumeh R, Jez JM, Kunkel BN. Indole-3-acetaldehyde dehydrogenase-dependent auxin synthesis contributes to virulence of Pseudomonas syringae strain DC3000. PLoS Pathog. 2018 Jan 2;14(1):e1006811. doi: 10.1371/journal.ppat.1006811., eCollection 2018 Jan. PMID:29293681 doi:http://dx.doi.org/10.1371/journal.ppat.1006811

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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