Inducible (class 3) aldehyde dehydrogenase from rat hepatocellular carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant relationship to the class 1 and 2 enzymes from mammalian liver cytosol/mitochondria

Abstract

Peptides from rat liver aldehyde dehydrogenase (AIDH) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment match the AIDH structure from HTC rat hepatoma cells (HTC-AIDH) at all positions examined, indicating induction of the same gene product by two independent routes. This 452 amino acid residue, class 3 AIDH structure differs substantially from the 500-residue AIDH structures isolated from normal liver cytosol (class 1) and mitochondria (class 2). Despite a 29.8% identity in 429 overlapping amino acids vs the human class 1 enzyme (27.7% vs class 2), neither the N- nor C-termini coincide, and gaps are introduced to optimize the alignment. Two residues placed in the active site of human liver AIDH by chemical modification, Cys-302 and Glu-268, are conserved in class 3 AIDH as Cys-243 and Glu-209. Cys-243/302 is the only cysteine residue conserved in all known AIDH structures. Gly-245 and Gly-250 of class 1/2 AIDHs, fitting the patterns of glycine residues in coenzyme binding fold of other dehydrogenases, are also conserved. Otherwise, Cys-49, Cys-162, and Glu-487, to which functional importance has also been ascribed, are not retained in the class 3 structure. Overall, a high conservation of Gly, Pro, and Trp and similar patterns of predicted secondary structure indicate general conservation of tertiary structure, as noted with other distantly related proteins. Three exon boundaries from the human liver mitochondria AIDH gene directly correspond to the N-terminus of the rat class 3 protein and to two of the gaps in the alignment.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural features of stomach aldehyde dehydrogenase distinguish dimeric aldehyde dehydrogenase as a ‘variable’ enzyme ‘Variable’ and ‘constant’ enzymes within the alcohol and aldehyde dehydrogenase families

“…The results confirm that stomach aldehyde dehydrollenase is identical to other dimeric aldehyde dehydrogenases known, tile inducible or tumor-derived enzyme, obtained from liver, bladder and other sources [2,, This is concluded from analysis of close to half the entire structure, and this type of aldehyde dehydrogenase is therefore now possible to compare for large parts of the structures from two different species, rat and human, revealing a species divergence at 18% of all positions, This divergence can be directly compared to that for other dehydrogenases of the same metabolic pathways, mitochondrial aldehyde dehydrogcnase, cytosolic aldehyde dehydrogenase classical alcohol dehydrogenase, class Ill alcohol dehydrogenase, and polyol dehydrogenase, all also known from human and rat (cf. .…”

“…Positions refer to those known for the entire structure of the tumor.derived rat dehydrogenase [2,11] while peptide designations DA-DJ refer Lo the Asp-cleavage products purified as sltown in …”

“…Alcohol and aldehyde dehydrogenases both exhibit considerable multiplicity with mammalian structures known for four [1] and three [2] 'classes', respectively, and with at least three additional mammalian enzymes [3][4][5][6] clearly belonging to these two families (sorbitol dehydrogenase and ~'-crystallin in the case of the alcohol dehydrogenase family; glutamic ,y-semialdehyde or l-pyrroline-5-carboxylate dehydrogenase in the case of the aldehyde dehydrogenase family). In both cases, most studies have concerned the liver enzymes, but alcohol and aldehyde dehydrogenases have wide-spread occurrence, and the two act ivities also occur in stomach, although only limited amounts of the enzymes have been available for study from this source.…”

“…In both cases, most studies have concerned the liver enzymes, but alcohol and aldehyde dehydrogenases have wide-spread occurrence, and the two act ivities also occur in stomach, although only limited amounts of the enzymes have been available for study from this source. Recently, however, the stomach alcohol dehydrogenase was established to constitute a new structural class, class IV [1], while the stomach aldehyde dehydrogenase has been concluded [7][8][9][10] to be identical to one of the already known aldehyde dehydrogenases, the form that is inducible or tumor-derived in liver [2,11] and also occurs in bladder [12]. Because of this difference between the stomach alcohol and aldehyde dehydrogenases, it is essential to characterize this aldehyde dehydrogenase further.…”

Critical Glutamic Acid Residues Affecting the Mechanism and Nucleotide Specificity of Vibrio Harveyi Aldehyde Dehydrogenase

“…As the nucleotide specificity and sequence of Vh. (Vedadi et al, 1995); C13rt, from 2,3,7,8,-tetrachlorodibenzo-p-dioxin induction of rat liver (class 3) (Hempel et al, 1989); C13mrt, from rat liver microsomes (class 3) (Miyauchi et al, 1991); Colialdh, from E. coli (Heim and Strehler, 1991); Spbtaldh, betaine ALDH from spinach (Weretilnyk and Hanson, 1990) ; Fothfaldh, formyl tetrahydrofolate dehydrogenase from rat liver (Cook et al, 1991); Ohmucsaldh, hydroxymuconic semialdehyde dehydrogenase from Pseudornonas (Norlund and Shingler, 1990); C1 Ihu, from human liver cytosol (Hempel et al, 1984); Cllrt, from phenobarbital induction of rat liver (Dunn et al, 1989); C12hu, from human liver mitochondria ; Aldhxhu, from human genomic library screening (Hsu and Chang, 1991); Mmalsaldh, methyl malonic semialdehyde dehydrogenase from rat liver (Kedishvilli et al, 1992); Aspraldh, from Aspergillus (Pickett et a]., 1987); Vchlaldh, from V cholera (Parsot and Mekalanos, 1991); Sucsaldh, succinyl semialdehyde dehydrogenase from E. coli (Niegmann et al, 1992; submission to SwissProt database, accession Gabd-Ecoli) ; Psudaldh, from Pseudomoms (Kok et al, 1989); Gglusaldh, Y-glutamyl semialdehyde dehydrogenase from yeast (Krzywicki and Brandriss, 1984 ALDH is quite different from other ALDHs, Glu253 was mutated to Ala and expressed in E. coli K38 to investigate whether the role of this residue is similar to that proposed for the comparable residue in mammalian ALDHs. The level of expression of the E253A mutant was as high as that for the recombinant Vh.…”