Abstract
Alcohol dehydrogenase is considered a very important enzyme in insect metabolism because it is involved (in its homodimeric form) in the catalysis of the reversible conversion of various alcohols in larval feeding sites to their corresponding aldehydes and ketones, thus contributing to detoxification and metabolic purposes. Using 14 amino acid ADH sequences recently determined in our laboratory, we constructed a three-dimensional (3D) model of olive fruit fly Bactrocera oleae ADH1 and ADH2, based on the known homologous Drosophila lebanonensis ADH structure, and the amino acid residues that have been proposed as being responsible for catalysis were located on it. Moreover, in a comparative study of the ADH sequences, the residues occupying characteristic positions in the ADH of species of the Bactrocera and Ceratitis genera (called genus-specific) as well as residues appearing only in ADH1 or ADH2 (called isozymic-specific) were defined and localized on the 3D model. All regions important for catalytic activity, such as those forming the substrate- and coenzyme-binding sites, are highly conserved in all tephritid species examined. Genus-specific amino acids are located on the outside of the protein, on loops and regions predicted to be antigenic. The higher percentage of genus-specific amino acid variation seems to be centered in the NAD adenine-binding site, located near the surface of the protein molecule. Nine of 12 isozymic-specific positions are lined along an “arc” on the surface of the protein, thus linking the two “monomer bases” of the dimer via the C-terminal interacting loops. Furthermore, the distribution of isozymic- and genus-specific amino acids on the monomer–monomer interface may have some evolutionary significance. Most amino acids predicted to be antigenic are positioned in peripheral regions of nonfunctional importance, but surprisingly, an additional antigenic region is contained within the (highly conserved in tephritids) C-terminal tail.
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References
R Albalat S Atrian R Gonzalez-Duarte (1994) ArticleTitle Drosophila lebanonensis ADH: Analysis of recombinant wild-type enzyme and site directed mutagenesis. The effect of restoring the consensus sequence in two positions. FEBS Lett 341 171–176 Occurrence Handle10.1016/0014-5793(94)80451-6 Occurrence Handle1:CAS:528:DyaK2cXksFaqur0%3D Occurrence Handle8137935
S Atrian R Gonzalez-Duarte (1982) Comparison of some biochemical features of the enzyme alcohol dehydrogenase in sixteen species of Drosophila. S Lakovaara (Eds) Advances in genetics, development and evolution of Drosophila. Plenum Press New York 251–261
S Atrian L Sanchez-Pulido R Gonzalez-Duarte A Valencia (1998) ArticleTitleShaping of Drosophila alcohol dehydrogenase through evolution: relationship with enzyme functionality. J Mol Evol 47 211–221 Occurrence Handle1:CAS:528:DyaK1cXltlagurY%3D Occurrence Handle9694670
P Batterham GK Chambers WT Starmer DT Sullivan (1984) ArticleTitleOrigin and expression of an alcohol dehydrogenase gene duplication in the genus Drosophila. Evolution 38 644–657 Occurrence Handle1:CAS:528:DyaL2cXlt1Olt7w%3D
DJ Begun (1997) ArticleTitleOrigin and evolution of a new gene descended from alcohol dehydrogenase in Drosophila. Genetics 145 375–382
J Benach S Atrian R Gonzalez-Duarte R Ladenstein (1998) ArticleTitleThe refined crystal structure of Drosophila lebanonensis alcohol dehydrogenase at 1.9 A resolution. J Mol Biol 282 383–399 Occurrence Handle10.1006/jmbi.1998.2015 Occurrence Handle9735295
J Benach S Atrian R Gonzalez-Duarte R Ladenstein (1999) ArticleTitleThe catalytic reaction and inhibition mechanism of Drosophila alcohol dehydrogenase: observation of an enzyme-bound NAD-ketone adduct at 1.4 A resolution by X-ray crystallography. J Mol Biol 289 335–355 Occurrence Handle10.1006/jmbi.1999.2765 Occurrence Handle10366509
J Benach S Atrian J Fibla R Gonzalez-Duarte R Ladenstein (2000) ArticleTitleStructure-function relationships in Drosophila melanogaster alcohol dehydrogenase allozymes ADHS, ADHF and ADHUF, and distantly related forms. Eur J Biochem 267 3613–3622 Occurrence Handle10.1046/j.1432-1327.2000.01390.x Occurrence Handle1:CAS:528:DC%2BD3cXksVKgt7c%3D Occurrence Handle10848978
J Benach S Atrian R Ladenstein R Gonzalez-Duarte (2001) ArticleTitleGenesis of Drosophila ADH: The shaping of the enzymatic activity from a SDR ancestor. Chem-Biol Interact 130–132 405–415 Occurrence Handle10.1016/S0009-2797(00)00265-9
P Benos N Tavernarakis S Brogna G Thireos C Savakis (2000) ArticleTitleAcquisition of a potential marker for insect transformation: Isolation of a novel alcohol dehydrogenase gene from Bactrocera oleae by functional complementation in yeast. Mol Gen Genet 263 90–95 Occurrence Handle10732677
C Benyajati N Spoerel H Haymerle M Ashburner (1983) ArticleTitleThe messenger RNA for Adh in D. melanogaster differs in its 5′ end in different developmental stages. Cell 33 125–133 Occurrence Handle6432335
HM Berman T Battistuz TN Bhat WF Bluhm PE Bourne K Burkhardt Z Feng GL Gilliland L Iype S Jain P Fagan J Marvin D Padilla V Ravichandran B Schneider N Thanki H Weissig JD Westbrook C Zardecki (2002) ArticleTitleThe Protein Data Bank. Acta Cryst D 58 899–890 Occurrence Handle10.1107/S0907444902003451
MK Brendskag JS McKinley-McKee JO Winberg (1999) ArticleTitle Drosophila lebanonensis alcohol dehydrogenase: pH dependence of the kinetic coefficients. Biochim Biophys Acta 1431 74–86 Occurrence Handle10209281
S Brogna M Ashburner (1997) ArticleTitleThe Adh-related gene of Drosophila melanogaster is expressed as a functional dicistronic messenger RNA: Multigenic transcription in higher organisms. EMBO J 16 2023–2031 Occurrence Handle10.1093/emboj/16.8.2023 Occurrence Handle9155028
S Brogna PV Benos G Gasperi C Savakis (2001) ArticleTitleThe Drosophila alcohol dehydrogenase gene may have evolved independently of the functionally homologous medfly, olive fly, and flesh fly genes. Mol Biol Evol 18 322–329 Occurrence Handle1:CAS:528:DC%2BD3MXhvVKrtr8%3D Occurrence Handle11230533
BR Brooks RE Bruccoleri BD Olafson DJ States S Swaminathan M Karplus (1983) ArticleTitleCHARMM, a program for macromolecular energy minimization and dynamics calculations. J Comput Chem 4 165–175
GK Chambers (1988) ArticleTitleThe Drosophila alcohol dehydrogenase gene-enzyme system. Adv Genet 25 39–107 Occurrence Handle1:CAS:528:DyaL1MXltF2ksg%3D%3D
Z Chen L Lu M Shirley WR Lee SH Chang (1990) ArticleTitleSite-directed mutagenesis of glycine-14 and two “critical” cysteinyl residues in Drosophila alcohol dehydrogenase. Biochemistry 29 1112–1118 Occurrence Handle1:CAS:528:DyaK3cXnt1yktA%3D%3D Occurrence Handle2108721
Z Chen WR Lee SH Chang (1991) ArticleTitleRole of aspartic acid 38 in the cofactor specificity of Drosophila alcohol dehydrogenase. Eur J Biochem 202 262–267
Z Chen JC Jiang ZG Lin WR Lee SH Chang (1993) ArticleTitleSite-specific mutagenesis of Drosophila alcohol dehydrogenase: Evidence for involvement of tyrosine-152 and lysine-156 in catalysis. Biochemistry 32 3342–3346 Occurrence Handle1:CAS:528:DyaK3sXhvVKrt78%3D Occurrence Handle8461298
Z Chen I Tsigelny WR Lee ME Baker SH Chang (1994) ArticleTitleAdding a positive charge at residue 46 of Drosophila alcohol dehydrogenase increases cofactor specificity for NADP+ FEBS Lett 356 81–85 Occurrence Handle10.1016/0014-5793(94)01234-2 Occurrence Handle1:CAS:528:DyaK2MXjtVSms7Y%3D Occurrence Handle7988726
SW Chenevert NG Fossett SH Chang I Tsigelny ME Baker WR Lee (1995) ArticleTitleAmino acids important on enzyme and dimmer stability for Drosophila alcohol dehydrogenase. Biochem J 308 419–423 Occurrence Handle1:CAS:528:DyaK2MXmtFeku7k%3D Occurrence Handle7772022
N Cols S Atrian J Benach R Ladenstein R Gonzalez-Duarte (1997) ArticleTitle Drosophila alcohol dehydrogenase evaluation of Ser139 site-directed mutants. FEBS Lett 413 191–193 Occurrence Handle10.1016/S0014-5793(97)00894-6 Occurrence Handle1:CAS:528:DyaK2sXlvVKks7c%3D Occurrence Handle9280279
JR David C Bocquet M Arens P Fouillet (1976) ArticleTitleBiological role of alcohol dehydrogenase in the tolerance of Drosophila melanogaster to aliphatic alcohols: utilization of an ADH-null mutant. Biochem Genet 14 989–997 Occurrence Handle1:CAS:528:DyaE2sXmvVKltg%3D%3D Occurrence Handle828053
J Felsenstein (1985) ArticleTitleConfidence limits on phylogenies: An approach using the bootstrap. Evolution 39 783–791
D Fischer C Barret K Bryson A Elofsson A Godzik D Jones KJ Karplus LA Kelley RM Maccallum K Pawowski B Rost L Rychlewski MJ Sternberg (1999) ArticleTitleCAFASP-1: Critical assessment of fully automated structure prediction methods. Proteins Struct Funct Genet Suppl 3 209–217 Occurrence Handle10.1002/(SICI)1097-0134(1999)37:3+<209::AID-PROT27>3.3.CO;2-P
RH Foote FL Blanc AL Norrbom (1993) Handbook of the fruit flies (Diptera: Tephritidae) of America north of Mexico. Comstock Ithaca, NY
G Gasperi L Baruffi A Malacrida AS Robinson (1992) ArticleTitleA biochemical genetic study of alcohol dehydrogenase isozymes of the Medfly Ceratitis capitata. Wied Biochem Genet 30 289–304 Occurrence Handle1:CAS:528:DyaK38Xks1Kqt74%3D
G Gasperi D Kafetzopoulos A Christodoulidou V Bouriotis C Savakis (1994) ArticleTitleIsolation and partial characterization of two alcohol dehydrogenase isozymes from the medfly Ceratitis capitata. Insect Biochem Mol Biol 24 87–94 Occurrence Handle10.1016/0965-1748(94)90126-0 Occurrence Handle8111424
BW Geer SW McKechnie ML Langevin (1986) ArticleTitleThe effect of dietary ethanol on the composition of lipids of Drosophila melanogaster larvae. Biochem Genet 24 51–69 Occurrence Handle1:CAS:528:DyaL28XitVKjtrY%3D Occurrence Handle2938574
D Ghosh Z Wawrzak CM Weeks WL Duax M Erman (1994) ArticleTitleThe refined three-dimensional structure of 3α, 20β-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases. Structure 2 629–640 Occurrence Handle1:CAS:528:DyaK2MXot1ersA%3D%3D Occurrence Handle7922040
JH Gillespie (1991) The causes of molecular evolution. Oxford University Press New York.
GN Goulielmos N Cosmidis M Loukas S Tsakas E Zouros (2001) ArticleTitleCharacterization of two alcohol dehydrogenase (Adh) loci from the olive fruit fly, Bactrocera (Dacus) oleae and implications for Adh duplication in dipteran insects. J Mol Evol 52 29–39 Occurrence Handle11139292
GN Goulielmos N Cosmidis M Theodorakopoulou M Loukas E Zouros (2003a) ArticleTitleTracing the history of an enzyme polymorphism: The case of alcohol dehydrogenase-2 (Adh-2) of the olive fruit fly Bactrocera oleae. Mol Biol Evol 20 293–306 Occurrence Handle10.1093/molbev/msg033 Occurrence Handle1:CAS:528:DC%2BD3sXisFaru7k%3D
GN Goulielmos M Loukas G Bondinas E Zouros (2003b) ArticleTitleThe evolutionary history of the alcohol dehydrogenase gene duplication in species of the family Tephritidae. J Mol Evol 57 170–180 Occurrence Handle10.1007/s00239-003-2464-z Occurrence Handle1:CAS:528:DC%2BD3sXmsFGrurY%3D
T Horio T Kube S Natori (1996) ArticleTitlePurification and cDNA cloning of the alcohol dehydrogenase of the flesh fly Sarcophaga penegrina. A structural relationship between alcohol dehydrogenase and a 25-kda protein. Eur J Biochem 237 698–703 Occurrence Handle8647115
H Jornvall M Persson J Jeffery (1981) ArticleTitleAlcohol and polyol dehydrogenase are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type. Proc Natl Acad Sci USA 78 4226–4230 Occurrence Handle7027257
HH Jornvall H von Bahr-Lindstrom G Jany W Ulmer M Froschle (1984) ArticleTitleExtended superfamily of short alcohol-polyol-sugar dehydrogenases: Structural similarities between glucose and ribitol dehydrogenases. FEBS Lett 165 190–196 Occurrence Handle6420186
H Jornvall B Persson M Krook S Atrian R Gonzalez-Duarte (1995) ArticleTitleShort-chain dehydrogenases/reductases (SDR) Biochemistry 34 6003–6013 Occurrence Handle7742302
M Kimura (1980) ArticleTitleA simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16 111–120 Occurrence Handle7463489
AS Kolaskar PC Tongaonkar (1990) ArticleTitleA semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett 276 172–174 Occurrence Handle1:CAS:528:DyaK3MXktVGntw%3D%3D Occurrence Handle1702393
PJ Kraulis (1991) ArticleTitleMOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J Appl Crystallogr 24 946–950 Occurrence Handle10.1107/S0021889891004399
S Kumar K Tamura IB Jakobsen M Nei (2001) ArticleTitleMEGA 2: Molecular Evolutionary Genetics Analysis software. Bioinformatics 17 1244–1245 Occurrence Handle1:CAS:528:DC%2BD38XmtVCktQ%3D%3D Occurrence Handle11751241
M Long CH Langley (1993) ArticleTitleNatural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. Science 266 IssueID5104 91–95
AR Malacrida G Gasperi A Zacharopoulou C Torti E Riva-Francos R Milani (1992) ArticleTitleEvidence for a genetic duplication involving alcohol dehydrogenase genes in Ceratitis capitata. Biochem Genet 30 35–48 Occurrence Handle1520253
JH McDonald M Kreitman (1991) ArticleTitleAdaptive protein evolution at the Adh locus in Drosophila. Nature 351 652–654 Occurrence Handle1:CAS:528:DyaK3MXks1yrtLs%3D Occurrence Handle1904993
JS McKinley J-O Winberg G Pettersson (1991) ArticleTitleMechanism of action of Drosophila alcohol dehydrogenase. Biochem Int 25 879–885 Occurrence Handle1804107
GK Meghlaoui M Veuille (1997) ArticleTitleSelection and methionine accumulation of the fat body protein 2 gene (FBP2), a duplicate of the Drosophila alcohol dehydrogenase. J Mol Evol 44 23–32 Occurrence Handle9010133
M Menotti-Raymond WT Starmer DT Sullivan (1991) ArticleTitleCharacterization of the structure and evolution of the Adh region of Drosophila hydei. Genetics 127 355–366 Occurrence Handle1:CAS:528:DyaK3MXlvF2qs7Y%3D Occurrence Handle2004708
EA Merrit DJ Bacon (1997) ArticleTitleRaster3D: Photorealistic Molecular Graphics. Methods Enzymol 277 505–524 Occurrence Handle1:CAS:528:DyaK2sXntFals7s%3D
A Nicholls KA Sharp B Honig (1991) ArticleTitleProtein folding and association—Insights from the interfacial and the thermodynamic properties of hydrocarbons. Proteins 11 281–296 Occurrence Handle1:CAS:528:DyaK38XhtVWgur4%3D Occurrence Handle1758883
DI Nurminsky EN Moriyama ER Lozovskaya DL Hartl (1996) ArticleTitleMolecular phylogeny and genome evolution in the Drosophila virilis species group: Duplications of the alcohol dehydrogenase gene. Mol Biol Evol 13 132–149 Occurrence Handle1:CAS:528:DyaK28XhtVylurg%3D Occurrence Handle8583887
WR Pearson DJ Lipman (1988) ArticleTitle. Proc Natl Acad Sci USA 85 2444–2448 Occurrence Handle1:CAS:528:DyaL1cXktFyit78%3D Occurrence Handle3162770
MC Peitsch (1995) ArticleTitleProMod: Automated knowledge-based protein modelling tool. PDB Q Newslett 72 4
B Persson M Krook H Jornvall (1991) ArticleTitleCharacteristics of short-chain alcohol dehydrogenases and related enzymes. Eur J Biochem 200 537–543 Occurrence Handle1:CAS:528:DyaK3MXkvVyht7w%3D Occurrence Handle1889416
. Quanta (1998) A molecular graphics program licensed to molecular simulations, . San Diego, CA
L Rat M Veuille J-A Lepesant (1991) ArticleTitle Drosophila fat body protein P6 and alcohol dehydrogenase are derived from a common ancestral protein. J Mol Evol 33 194–203 Occurrence Handle1:CAS:528:DyaK38Xit12hu74%3D Occurrence Handle1920455
de Ribas L Pouplana L Fothergill-Gilmore (1994) ArticleTitleThe active site architecture of a short-chain dehydrogenase defined by site- directed mutagenesis and structure modeling. Biochemistry 33 7047–7055 Occurrence Handle8003469
P Rice I Longden A Bleasby (2000) ArticleTitleEMBOSS: The European Molecular Biology Open Software Suite. Trends Genet 16 276–277 Occurrence Handle10827456
MG Rossmann A Liljas C-I Branden LJ Banaszac (1975) The detection of sub-units within the crystallographic asymmetric unit. In: Boyer PD (ed) The enzymes, 3rd ed, Vol XIA. Academic Press Orlando, FL 61–102
N Saitou M Nei (1987) ArticleTitleThe neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 4 406–425 Occurrence Handle1:STN:280:BieC1cbgtVY%3D Occurrence Handle3447015
C Savakis M Ashburner JH Willis (1986) ArticleTitleThe expression of the gene coding for alcohol dehydrogenase during the development of Drosophila melanogaster. Dev Biol 114 194–207 Occurrence Handle1:CAS:528:DyaL28Xhs1Gktbw%3D
NS Scrutton A Berry RN Perham (1990) ArticleTitleRedesign of coenzyme specificity of a dehydrogenase by protein engineering. Nature 343 38–43 Occurrence Handle1:CAS:528:DyaK3cXhslClsrk%3D Occurrence Handle2296288
PHA Sneath RR Sokal (1973) ArticleTitleNumerical taxonomy. Freeman, San Francisco Sofer W, Ursprung H (1968) Drosophila alcohol dehydrogenase. J Biol Chem 243 3110–3115
DT Sullivan PW Atkinson WT Starmer (1989) ArticleTitleMolecular evolution of the alcohol dehydrogenase genes in the genus Drosophila. Evol Biol 24 107–147
N Tanaka T Nonaka T Tanabe T Yoshimoto D Tsuru Y Mitsui (1996) ArticleTitleCrystal structures of the binary and ternary complexes of 7β-hydroxysteroid dehydrogenases from Escherichia coli. Biochemistry 35 7715–7730 Occurrence Handle10.1021/bi951904d Occurrence Handle1:CAS:528:DyaK28XjtFyrt74%3D Occurrence Handle8672472
DR Thatcher (1980) ArticleTitleThe complete aminoacid sequence of three alcohol dehydrogenase alleloenzymes (AdhN-11, AdhS and AdhUF) from the fruitfly Drosophila melanogaster. Biochem J 187 875–883 Occurrence Handle1:CAS:528:DyaL3cXmtVSjtb4%3D Occurrence Handle6821373
JD Thompson TJ Gibson F Plewniak F Jeanmougin DG Higgins (1997) ArticleTitleThe ClustalX windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 24 4876–4882 Occurrence Handle10.1093/nar/25.24.4876
RK Wierenga MCH De Maeyer WGJ Hoi (1985) ArticleTitleInteraction of pyrophosphate moieties with α-helices in dinucleotide binding proteins. Biochemistry 24 1346–1357 Occurrence Handle1:CAS:528:DyaL2MXhsVGhu7w%3D
J-O Winberg R Hovik JS McKinley-McKee E Juan R Gonzalez-Duarte (1986) ArticleTitleBiochemical properties of alcohol dehydrogenase from Drosophila lebanonensis. Biochem J 235 481–490 Occurrence Handle1:CAS:528:DyaL28Xit1Wit7c%3D Occurrence Handle2943270
J-O Winberg MK Brendskag I Sylte RI Lindstad JS McKinley-McKee (1999) ArticleTitleThe catalytic triad in Drosophila alcohol dehydrogenase: pH, temperature and molecular modelling studies. J Mol Biol 294 601–616 Occurrence Handle10.1006/jmbi.1999.3235 Occurrence Handle1:CAS:528:DyaK1MXotFeku7w%3D Occurrence Handle10610783
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Eliopoulos, E., Goulielmos, G.N. & Loukas, M. Functional Constraints of Alcohol Dehydrogenase (ADH) of Tephritidae and Relationships with Other Dipteran Species . J Mol Evol 58, 493–505 (2004). https://doi.org/10.1007/s00239-003-2568-5
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DOI: https://doi.org/10.1007/s00239-003-2568-5