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

Yin, Shih‐Jiun; Vagelopoulos, Nikolaos; Wang, Sung-Ling; Jörnvall, Hans

doi:10.1016/0014-5793(91)80559-l

Cited by 38 publications

(19 citation statements)

References 18 publications

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“…1). Obviously, this overall pattern constitutes the explanation to the presence of two types of variability observed in some dehydrogenases [6]. The two types are concluded to reflect differences in functional restrictions on the structures, and the results now show that the 'constant' dehydrogenase pattern is the one with many representatives closely assembled at about the same value ( Fig.…”

Section: Resultsmentioning

confidence: 59%

“…Many dehydrogenases, however, appear to follow either of two separate evolutionary lines, being 'constant' or 'variable', with such a split also between related forms with seemingly similar properties [6]. For evaluation of which of the dehydrogenase patterns that is typical at large, and what the split may mean, comparisons with the patterns for other proteins are of interest.…”

Section: Introductionmentioning

confidence: 99%

“…In the case of dehydrogenases, two variability patterns, constant and variable, have been noticed [6], but at that stage it was unclear which was the common alternative. We can now see that the constant pattern appears to be the one with many representatives centred at about the same value (6%, Fig.…”

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confidence: 99%

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Variability patterns of dehydrogenases versus peptide hormones and proteases/antiproteases

1993

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Comparisons of human/rat species variants of 23 dehydrogenases versus 41 entries for peptide hormones and 41 for proteasesfantiproteases reveal characteristic patterns. Dehydrogenases are 'constant' (2-88 residue differences between homologues) or 'variable' (1240% differences). Peptide hormones exhibit a wider range, with many 'strictly conserved' and others spreading upscale, while proteases/antiproteases are overall shifted upscale, with few 'constant' and many 'variable'. Overall, the influence of polypeptide size and function is confirmed, while for the dehydrogenases, the data highlight the 'constant' pattern as the one with high frequency values and suggest for classic liver alcohol dehydrogenase the 'variable' pattern to correlate with emerging functions.

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Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Variability patterns of dehydrogenases versus peptide hormones and proteases/antiproteases

1993

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“…It differs from classes I, II, III, and V (55-68% residue identities), much as they differ from each other (59-64% identities). The rat/human differences vary between the classes (38), but in all cases the present structure differs much more than do isozymes or mammalian species variants (Table 1).…”

Section: Methodsmentioning

confidence: 94%

Mammalian class IV alcohol dehydrogenase (stomachalcohol dehydrogenase): structure, origin, and correlation withenzymology.

Parés

Cederlund

Moreno

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The structure of a mammalian class IV alcohol dehydrogenase has been determined by peptide analysis of the protein isolated from rat stomach. The structure indicates that the enzyme constitutes a separate alcohol dehydrogenase class, in agreement with the distinct enzymatic properties; the class IV enzyme is somewhat closer to class I (the "classical" liver alcohol dehydrogenase; -68% residue identities) than to the other classes (II, m, and V; -60% residue identities), suggesting that class IV might have originated through duplication of an early vertebrate class I gene. The activity of the class IV protein toward ethanol is even higher than that of the classical liver enzyme. Both Km and kalt values are high, the latter being the highest of any class characterized so far. Structurally, these properties are correlated with replacements at the active site, affecting both substrate and coenzyme binding. In particular, Ala-294 (instead of valine) results in increased space in the middle section of the substrate cleft, Gly-47 (instead of a basic residue) results in decreased charge interactions with the coenzyme pyrophosphate, and Tyr-363 (instead of a basic residue) may also affect coenzyme binding. In combination, these exchanges are compatible with a promotion of the off dissociation and an increased turnover rate. In contrast, residues at the inner part of the substrate cleft are bulky, accounting for low activity toward secondary alcohols and cyclohexanol. Exchanges at positions 259-261 involve minor shifts in glycine residues at a reverse turn in the coenzyme-binding fold. Clearly, class IV is distinct in structure, ethanol turnover, stomach expression, and possible emergence from class I.

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“…It establishes that class I alcohol dehydrogenase, although characteristically more variable than several other dehydrogenases [17], has undergone a fairly constant rate of evolutionary changes in different branches of the vertebrate radiation. Pairwise residue differences between divergent lines are presently found at close to 10% of the positions/100 million years.…”

Section: Discussionmentioning

confidence: 95%

Basic features of class‐I alcohol dehydrogenase: variable and constant segments coordinated by inter‐class and intra‐class variability

Persson

Bergman

Keung

et al. 1993

European Journal of Biochemistry

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The enzymatic and structural properties of alligator liver alcohol dehydrogenase have been determined. Aliphatic and alicyclic alcohols serve as substrates for this first reptilian form of the enzyme characterized, with K,, values decreasing rapidly from methanol to hexanol, as for the human class I enzymes, and a K,, of 1.2 mM for ethanol at pH 9.9. The N-terminus of the 374-residue protein chain is acetyl-blocked.The enzyme is related in descending order to class I > 111 > V > I1 of the structurally characterized mammalian alcohol dehydrogenases. This observation is compatible with the presence of a I/III ancestral line. Differences of the enzyme classes exceed those of the species, suggesting an early origin of the classes. Within its enzyme class, the reptilian protein is most closely related to the avian form (82% residue identities), and is closer to the human than to the amphibian form (76%, versus 69%, respectively). This establishes class I alcohol dehydrogenase as an enzyme having fairly constant rate of change during much of vertebrate evolution, -10% residue differences/lOO million years of separation between pairs compared.Residues interacting with the substrate and coenzyme are largely conserved. In the alligator enzyme, there are only four replacements in the substrate pocket compared with the human class I y subunit, and those are not known to have functional roles. These properties account for the kinetic parameters, and suggest distinct metabolic functions for the class I enzyme in vertebrates.Comparisons of the enzymes of the different vertebrate lines reveal that segment patterns are characteristic features of the class I enzymes.

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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

Cited by 38 publications

References 18 publications

Variability patterns of dehydrogenases versus peptide hormones and proteases/antiproteases

Variability patterns of dehydrogenases versus peptide hormones and proteases/antiproteases

Mammalian class IV alcohol dehydrogenase (stomachalcohol dehydrogenase): structure, origin, and correlation withenzymology.

Basic features of class‐I alcohol dehydrogenase: variable and constant segments coordinated by inter‐class and intra‐class variability

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