Characteristics of short-chain alcohol dehydrogenases and related enzymes.

Different short-chain dehydrogenases are distantly related, constituting a protein family now known from at least 20 separate enzymes characterized, but with extensive differences, especially in the C-terminal third of their sequences. Many of the first known members were prokaryotic, but recent additions include mammalian enzymes from placenta, liver and other tissues, including 15-hydroxyprostaglandin, 17 beta-hydroxysteroid and 11 beta-hydroxysteroid dehydrogenases. In addition, species variants, isozyme-like multiplicities and mutants have been reported for several of the structures. Alignments of the different enzymes reveal large homologous parts, with clustered similarities indicating regions of special functional/structural importance. Several of these derive from relationships within a common type of coenzyme-binding domain, but central-chain patterns of similarity go beyond this domain. Total residue identities between enzyme pairs are typically around 25%, but single forms deviate more or less (14-58%). Only six of the 250-odd residues are strictly conserved and seven more are conserved in all but single cases. Over one third of the conserved residues are glycine, showing the importance of conformational and spatial restrictions. Secondary structure predictions, residue distributions and hydrophilicity profiles outline a common, N-terminal coenzyme-binding domain similar to that of other dehydrogenases, and a C-terminal domain with unique segments and presumably individual functions in each case. Strictly conserved residues of possible functional interest are limited, essentially only three polar residues. Asp64, Tyr152 and Lys156 (in the numbering of Drosophila alcohol dehydrogenase), but no histidine or cysteine residue like in the completely different, classical medium-chain alcohol dehydrogenase family. Asp64 is in the suggested coenzyme-binding domain, whereas Tyr152 and Lys156 are close to the center of the protein chain, at a putative inter-domain, active-site segment. Consequently, the overall comparisons suggest the possibility of related mechanisms and domain properties for different members of the short-chain family.

[1]  H. Jörnvall,et al.  Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[2]  K. Jany,et al.  Complete amino acid sequence of glucose dehydrogenase from Bacillus megaterium , 1984, FEBS letters.

[3]  H. Jörnvall,et al.  Extended superfamily of short alcohol‐polyol‐sugar dehydrogenases: structural similarities between glucose and ribitol dehydrogenases , 1984, FEBS letters.

[4]  S. Taylor,et al.  Ribitol dehydrogenase of Klebsiella aerogenes. Sequence and properties of wild-type and mutant strains. , 1985, The Biochemical journal.

[5]  L. Sawyer,et al.  Secondary-structure prediction from the sequence of Drosophila melanogaster (fruitfly) alcohol dehydrogenase. , 1980, The Biochemical journal.

[6]  F. Wold,et al.  Butyl isocyanate, an active-site-specific reagent for yeast alcohol dehydrogenase. , 1973, Biochemistry.

[7]  B. Persson,et al.  Eye lens zeta-crystallin relationships to the family of "long-chain" alcohol/polyol dehydrogenases. Protein trimming and conservation of stable parts. , 1989, Biochemistry.

[8]  F. Debellé,et al.  Nucleotide sequence of Rhizobium meliloti RCR2011 genes involved in host specificity of nodulation. , 1986, Nucleic acids research.

[9]  D. Thatcher.  The complete amino acid sequence of three alcohol dehydrogenase alleloenzymes (AdhN-11, AdhS and AdhUF) from the fruitfly Drosophila melanogaster. , 1980, The Biochemical journal.

[10]  H. Jörnvall,et al.  The primary structure of alcohol dehydrogenase from Drosophila lebanonensis. Extensive variation within insect 'short-chain' alcohol dehydrogenase lacking zinc. , 1989, European journal of biochemistry.

[11]  P. Hylemon,et al.  Evidence for a multigene family involved in bile acid 7-dehydroxylation in Eubacterium sp. strain VPI 12708 , 1988, Journal of bacteriology.

[12]  S. Hallam,et al.  Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. , 1988, Gene.

[13]  M. Saier,et al.  Glucitol-specific enzymes of the phosphotransferase system in Escherichia coli. Nucleotide sequence of the gut operon. , 1987, The Journal of biological chemistry.

[14]  B. Vallee,et al.  ACTIVE-CENTER PEPTIDES OF LIVER-ALCOHOL DEHYDROGENASE. I. THE SEQUENCE SURROUNDING THE ACTIVE CYSTEINYL RESIDUES. , 1964, Biochemistry.

[15]  H. Jörnvall,et al.  Modification of Alcohol Dehydrogenases with a Reactive Coenzyme Analogue , 1975 .

[16]  G. Ringold,et al.  A growth factor-repressible gene associated with protein kinase C- mediated inhibition of adipocyte differentiation , 1988, The Journal of cell biology.

[17]  P. Argos.  Computer analysis of protein structure. , 1990, Methods in enzymology.

[18]  Anders Liljas,et al.  2 Evolutionary and Structural Relationships among Dehydrogenases , 1975 .

[19]  J. C. Warren,et al.  Affinity labeling of steroid binding sites. Study of the active site of 20-beta-hydroxysteroid dehydrogenase with 6-beta- and 11 alpha-bromoacetoxyprogesterone. , 1973, The Journal of biological chemistry.

[20]  J. Winberg,et al.  The AdhS alleloenzyme of alcohol dehydrogenase from Drosophila melanogaster. Variation of kinetic parameters with pH. , 1988, The Biochemical journal.

[21]  R. Wierenga,et al.  INTERACTION OF PYROPHOSPHATE MOIETIES WITH ALPHA-HELIXES IN DINUCLEOTIDE BINDING-PROTEINS , 1985 .

[22]  H. Jörnvall,et al.  Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. , 1990, Biochemistry.

[23]  H. Jörnvall,et al.  Characteristics of mammalian class III alcohol dehydrogenases, an enzyme less variable than the traditional liver enzyme of class I. , 1989, Biochemistry.

[24]  R. Vihko,et al.  Complete amino acid sequence of human placental 17β‐hydroxysteroid dehydrogenase deduced from cDNA , 1988, FEBS letters.

[25]  H. Jörnvall,et al.  Prokaryotic 20β‐hydroxysteroid dehydrogenase is an enzyme of the ‘short‐chain, non‐metalloenzyme’ alcohol dehydrogenase type , 1990, FEBS letters.

[26]  P. White,et al.  Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase. , 1989, The Journal of biological chemistry.

[27]  X. Parés,et al.  Class IV mammalian alcohol dehydrogenase , 1990, FEBS letters.

[28]  M. Takagi,et al.  Nucleotide sequencing and characterization of the genes encoding benzene oxidation enzymes of Pseudomonas putida , 1987, Journal of bacteriology.

[29]  H. Eklund,et al.  Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate binding pockets. , 1990, European Journal of Biochemistry.

[30]  P. Hylemon,et al.  Nucleotide sequence and regulation of a gene involved in bile acid 7-dehydroxylation by Eubacterium sp. strain VPI 12708 , 1988, Journal of bacteriology.

[31]  H. Hennecke,et al.  The symbiotic nitrogen fixation regulatory operon (fixRnifA) of Bradyrhizobium japonicum is expressed aerobically and is subject to a novel, nifA-independent type of activation. , 1987, Nucleic acids research.

[32]  H. Eklund,et al.  3 Alcohol Dehydrogenases , 1975 .

[33]  H. Jörnvall,et al.  Pseudomonas 3β‐hydroxysteroid dehydrogenase , 1991 .

[34]  B. Aronson,et al.  The primary structure of Escherichia coli L-threonine dehydrogenase. , 1989, The Journal of biological chemistry.

[35]  A. Sinskey,et al.  Poly-beta-hydroxybutyrate biosynthesis in Alcaligenes eutrophus H16. Characterization of the genes encoding beta-ketothiolase and acetoacetyl-CoA reductase. , 1989, The Journal of biological chemistry.

[36]  J. C. Warren,et al.  Affinity labeling of steroid binding sites. Synthesis of 16 -bromoacetoxyprogesterone and its use for affinity labeling of 20 -hydroxysteroid dehydrogenase. , 1972, The Journal of biological chemistry.

[37]  Z. Chen,et al.  Site-directed mutagenesis of glycine-14 and two "critical" cysteinyl residues in Drosophila alcohol dehydrogenase. , 1990, Biochemistry.

[38]  A. Sinskey,et al.  Fine structural analysis of the Zoogloea ramigera phbA‐phbB locus encoding β‐ketothiolase and acetoacetyl‐CoA reductase: nucleotide sequence of phbB , 1989, Molecular microbiology.

[39]  Ieuan Harris.  Structure and Catalytic Activity of Alcohol Dehydrogenases , 1964, Nature.

[40]  Y. Lachance,et al.  Full Length cDNA Structure and Deduced Amino Acid Sequence of Human β-Hydroxy-5-Ene Steroid Dehydrogenase , 1989 .

[41]  B. Persson,et al.  Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases. , 1987, European journal of biochemistry.

[42]  D. Gibson,et al.  Toluene degradation by Pseudomonas putida F1. Nucleotide sequence of the todC1C2BADE genes and their expression in Escherichia coli. , 1989, The Journal of biological chemistry.

[43]  K. Furukawa,et al.  Nucleotide sequence of the 2,3-dihydroxybiphenyl dioxygenase gene of Pseudomonas pseudoalcaligenes , 1987, Journal of bacteriology.

[44]  R. Scopes.  An iron‐activated alcohol dehydrogenase , 1983, FEBS letters.

[45]  H. Eklund,et al.  Molecular aspects of functional differences between alcohol and sorbitol dehydrogenases. , 1985, Biochemistry.

[46]  J. Liu,et al.  Nucleotide sequence of a cluster of Escherichia coli enterobactin biosynthesis genes: identification of entA and purification of its product 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase , 1989, Journal of bacteriology.

[47]  K. R. Woods,et al.  Prediction of protein antigenic determinants from amino acid sequences. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[48]  R. Strickler,et al.  Affinity labeling of steroid binding sites. Synthesis of 21-bromoacetylaminoprogesterone and study of 20beta-hydroxysteroid dehydrogenase. , 1978, The Journal of biological chemistry.

[49]  M. Baker,et al.  SEQUENCES OF INTEREST: Human Placental 17β-Hydroxysteroid Dehydrogenase is Homologous to NodG Protein of Rhizobium meliloti , 1989 .

[50]  M. Fukuda,et al.  Cloning and sequencing of the gene encoding the 72-kilodalton dehydrogenase subunit of alcohol dehydrogenase from Acetobacter aceti , 1989 .

[51]  H. Jörnvall,et al.  Structural analyses of mutant and wild-type alcohol dehydrogenases from drosophila melanogaster. , 1976, European journal of biochemistry.