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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_1nzx| PDB=1nzx | SIZE=400| SCENE=Aldehyde_dehydrogenase/Aldh/1 |right|CAPTION=Human aldehyde hydrogenase class 2 complex with NAD , [[1nzx]] }}
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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. 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. Glyceraldehyde-3-phophate (G3P)-ALDH is called GAPDH.
| | == Function == |
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| {{TOC limit|limit=2}}
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| == 3D Structures of Aldehyde dehydrogenase == | |
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| ''Update November 2011''
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| ===ALDH class 1===
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| [[3fx4]] – ALDH1 + NADP + inhibitor – pig<BR />
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| [[1bxs]] – ALDH1 - sheep<br />
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| [[1o9j]] – ALDH1 + NAD – Elephant shrew<br />
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| [[3rhj]], [[3rhl]], [[3rho]], [[3rhp]], [[3rhq]], [[3rhr]] – rALDH1 C- terminal (mutant) + NADP – rat<br />
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| [[3rhm]] - rALDH1 C- terminal
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| ===ALDH class 2===
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| [[3n80]], [[1o05]] – hALDH2 residues 18-517- human<BR />
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| [[3n81]], [[2onn]], [[2ono]], [[1zum]] – hALDH2 residues 18-517 (mutant) <BR />
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| [[1ag8]] – bALDH NAD binding domain - bovine
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| ''Binary complex''
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| [[3inj]], [[3inl]] - hALDH2 residues 18-517 + agonist<BR />
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| [[2vle]] - hALDH2 residues 24-517 + daidzin<BR />
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| [[1nzx]], [[1nzz]], [[1o00]], [[1o02]], [[1cw3]] - hALDH2 residues 18-517 + NAD<BR />
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| [[3n82]], [[3n83]], [[2onm]], [[2onp]], [[1nzw]], [[1o04]] – hALDH2 residues 18-517 (mutant) + NADH<BR />
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| [[3sz9]] - hALDH2 residues 18-517 + inhibitor<br />
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| [[1a4z]] – bALDH2 NAD-binding domain + NAD<BR />
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| ''Ternary complex''
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| [[1o01]] - hALDH2 residues 18-517 + NADH + aldehyde
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| ===ALDH class 3===
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| [[1ad3]] – rALDH<br />
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| [[3sza]] - hALDH<br />
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| [[3qj5]], [[3szb]] – hALDH + inhibitor
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| ===NAD-dependent ALDH===
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| [[2w8n]], [[2w8o]], [[2w8r]] – Succinate–semi-hALDH family 5<BR />
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| [[2w8p]] - Succinate–semi-hALDH family 5 (mutant) <BR />
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| [[3r31]] – Betaine-ALDH – ''Agrobacterium tumefaciens''<BR />
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| [[3ed6]] - Betaine-SaALDH – ''Staphylococcus aureus''<BR />
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| [[1a4s]] - Betaine-cALDH - cod<BR />
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| [[3llg]] – Aspartate-semi-MtALDH<BR />
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| [[2cq8]] - Formyltetrahydrofolate-hALDH PP-binding domain - NMR<BR />
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| [[2nac]] – Formate-PsALDH<BR />
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| [[3i44]] – ALDH – ''Bartonella henselae''<BR />
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| [[3ek1]] – ALDH – ''Brucella melitensis''<br />
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| [[3ros]] – ALDH – ''Lactobacillus acidophilus''<br />
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| [[3r64]] – ALDH – ''Corynebacterium glutamicum''<br />
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| [[3rhe]] – Benzaldehyde-ALDH – ''Legionella pneumophila''<br />
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| [[3u4j]] – ALDH – ''Sinorhizobium meliloti''
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| ''Binary complexes''
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| [[2w8q]] - Succinate–semi-hALDH family 5 + succinic acid<BR />
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| [[3fg0]] - Betaine-SaALDH + NAD<BR />
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| [[1bpw]] - Betaine-cALDH + NAD<BR />
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| [[2j6l]] – Aminoadipate-semi-hALDH family 7 + NAD<BR />
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| [[2cfi]] - Formyltetrahydrofolate-hALDH hydrolase domain + formyltetrahydropterin<BR />
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| [[2nad]] - Formate-PsALDH + NAD – ''Pseudomonas''<BR />
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| [[1bi9]] – Retinal-rALDH2 + NAD<BR />
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| [[3l4p]], [[1sij]] – ALDH + AsO3 – ''Desulfovibrio gigas''
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| ''Ternary complexes''
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| [[2gsd]] – Formate-ALDH + NAD + azide – ''Moraxella''<BR />
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| [[1nvm]] – Acetaldehyde-PsALDH + 4-hydroxy-oxovalerate aldolase + NAD<BR />
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| [[1llu]] - PaALDH + NAD + alcohol – ''Pseudomonas aeruginosa''
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| ===NAD-dependent glyceraldehyde-3-phosphate dehydrogenase===
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| [[1vsu]] – CpGAPDH – ''Cryptosporidium parvum''<BR />
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| [[1ywg]] – PfGAPDH – ''Plasmodium falciparum''<BR />
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| [[3cmc]] - GAPDH – ''Bacillus stearothermophilus''<BR />
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| [[2ep7]] – GAPDH – ''Aquifex aeolicus''<BR />
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| [[2i5p]] – GAPDH – ''Kluyveromyces marxianus''<BR />
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| [[1obf]] – GAPDH – ''Achromobacter xylosoxidans''<BR />
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| [[1crw]] – PvGAPDH – ''Palinurus versicolor''<BR />
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| [[1b7g]] – GAPDH – ''Sulfolobus solfataricus''<BR />
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| [[2gd1]] – GsGAPDH – ''Geobacillus stearothermophilus''<BR />
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| [[3e6a]] – OsGAPDH – ''Oryza sativa''<BR />
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| [[4gpd]], [[1gpd]] – GAPDH – lobster<BR />
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| [[3l6o]], [[3lc7]] – SaGAPDH<BR />
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| [[1dc3]], [[1dc5]], [[1s7c]] – EcGAPDH - ''Escherichia coli''
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| ''GAPDH binary complex''
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| [[1k3t]] - TcGAPDH + inhibitor<BR />
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| [[3hja]] - GAPDH + NAD – ''Borellia burgdorferi''<BR />
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| [[1vsv]], [[3cps]] - CpGAPDH + NAD<BR />
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| [[2vyn]], [[2vyv]] - rGAPDH residues 102-432 + EcGAPDH + NAD<BR />
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| [[2b4r]], [[2b4t]] – PfGAPDH (mutant) + NAD<BR />
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| [[1j0x]] – GAPDH + NAD – rabbit<BR />
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| [[1ihx]] – PvGAPDH + NAD<BR />
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| [[1dss]], [[1szj]] - PvGAPDH NAD-binding and catalytic domains+ NAD<BR />
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| [[1ihy]] – PvGAPDH + ADP-ribose<BR />
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| [[1gyq]], [[1gyp]] - LmGAPDH + NAD derivative – ''Leishmania mexicana''<BR />
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| [[1i32]], [[1i33]] – LmGAPDH + inhibitor<BR />
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| [[1a7k]] – LmGAPDH + NAD<BR />
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| [[1cer]], [[2g82]] - GAPDH + NAD – ''Thermus aquaticus''<BR />
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| [[1gd1]] - GsGAPDH + NAD<BR />
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| [[1npt]], [[1nq5]], [[1dbv]], [[2dbv]], [[3dbv]], [[4dbv]] - GsGAPDH (mutant) + NAD<BR />
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| [[3e5r]] – OsGAPDH + NAD<BR />
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| [[3k73]], [[3lvf]] – SaGAPDH + NAD<BR />
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| [[3lc2]] - SaGAPDH + G3P<BR />
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| [[3k9q]], [[3ksd]], [[3lc1]], [[3hq4]] - SaGAPDH (mutant) + NAD<BR />
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| [[3gpd]], [[1u8f]], [[1znq]] – hGAPDH + NAD<BR />
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| [[1gad]], [[1dc6]] - EcGAPDH + NAD<BR />
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| [[1gae]] - EcGAPDH (mutant) + NAD<BR />
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| [[1dc4]] – EcGAPDH + G3P<BR />
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| ''GAPDH ternary complex''
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| [[3id5]], [[3dmt]], [[1ml3]] – TcGAPDH + NAD + inhibitor – ''Trypanosoma cruzi''<BR />
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| [[1qxs]] - TcGAPDH + NAD + G3P analog<BR />
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| [[3cif]] - CpGAPDH + NAD + G3P<BR />
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| [[1nqa]], [[1nqo]] - GsGAPDH (mutant) + NAD + G3P<BR />
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| [[3ksz]], [[3kv3]], [[3l4s]] - SaGAPDH (mutant) + NAD + G3P<BR />
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| ===NADP-dependent ALDH===
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| [[3k2w]] - Betaine-ALDH – ''Pseudoalteromonas atlantica''<BR />
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| [[2hg2]], [[2opx]] – Lactaldehyde-EcALDH <BR />
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| [[2o2p]] – Formyltetrahydrofolate-rALDH C-terminal<br />
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| [[2y51]], [[2y52]], [[2y53]], [[2y5d]] – BxALDH (mutant) – ''Burkholderia xenovorans''<br />
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| [[3ifg]], [[3ifh]] - Succinate–semi-ALDH – ''Burkholderia pseudomallei''<br />
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| [[3rh9]] - Succinate–semi-ALDH – ''Marinobacter aquaeolei''
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| ''Binary complexes''
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| [[2wox]], [[2wme]], [[2xdr]], [[3zqa]] - Betaine-PaALDH + NADP<BR />
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| [[3lv1]] – Benzaldehyde-PpALDH3 + NADP – ''Pseudomonas putida''<BR />
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| [[2ilu]] - Lactaldehyde-EcALDH + NADP<BR />
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| [[3rhd]] - Lactaldehyde-MjALDH + NADP - ''Methanocaldococcus jannaschii''<br />
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| [[2o2q]], [[2o2r]] - Formyltetrahydrofolate-rALDH C-terminal + NADP<BR />
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| [[3b4w]] - MtALDH + NADP – ''Mycobacterium tuberculosis''<BR />
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| [[1eyy]], [[1ez0]] – ALDH + NADP – ''Vibrio harveyi''<br />
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| [[3jz4]] - Succinate–semi-EcALDH + NADP
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| ''Ternary complexes''
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| [[3lns]] - Benzaldehyde-PpALDH3 + NADP + benzoate<BR />
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| [[2imp]] - Lactaldehyde-EcALDH + NADH + lactate<BR />
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| [[2vro]] – BxALDH + NADP + alcohol
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| ===NADP-dependent glyceraldehydes-3-phosphate dehydrogenase===
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| [[1euh]] - SmGAPDH – ''Streptococcus mutans''<BR />
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| [[1qi6]] - SmGAPDH (mutant)
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| ''GAPDH binary complex''
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| [[2euh]] - SmGAPDH + NADP<BR />
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| [[2yyy]] – MjGAPDH + NADP <BR />
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| [[2pkq]] - spGAPDH subunit A, B + NADP – spinach<BR />
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| [[2pkr]], [[1rm4]], [[1jn0]] - spGAPDH subunit A + NADP<BR />
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| [[1rm3]], [[1rm5]] - spGAPDH subunit A (mutant) + NADP<BR />
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| [[2czc]] – GAPDH + NADP – ''Pyrococcus horikoshii''
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| ''GAPDH ternary complex''
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| [[2esd]], [[1qi1]] – SmGAPDH (mutant) + NADP + G3P<BR />
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| 3k9d – ALDH – ''Listeria monocytogenes''
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| ===Antiquitin===
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| [[2jg7]] – Antiquitin – Acanthopagrus schlegeli
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| [[3my7]] – ALDH – ''Vibrio parahaemolyticus''
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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 /> |
| | * '''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 /> |
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| | See also: |
| | *[[Pyrroline-5-carboxylate dehydrogenase]] |
| | *[[Succinate-semialdehyde dehydrogenase]] |
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| | == Disease == |
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| | 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. |
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| | == Relevance == |
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| | Buildup of toxic aldehydes causes cell damage and cardiac diseases. |
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| | == Structural highlights == |
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| | 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>. |
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| | == 3D Structures of aldehyde dehydrogenase == |
| | [[Aldehyde dehydrogenase 3D structures]] |
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| | </StructureSection> |
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| | ==References== |
| | {{reflist}} |
| | <references/> |
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| [[Category:Topic Page]] | | [[Category:Topic Page]] |
