DB code: S00319

RLCP classification 9.1050.440000.8010 : Hydride transfer
9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.1
CSA
M-CSA
MACiE M0255

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P10807 Alcohol dehydrogenase
EC 1.1.1.1
PF00106 (adh_short)
[Graphical View]
P00334 Alcohol dehydrogenase
EC 1.1.1.1
PF00106 (adh_short)
[Graphical View]
NP_001027266.1 (Protein)
NM_001032095.1 (DNA/RNA sequence)
NP_001027267.1 (Protein)
NM_001032096.1 (DNA/RNA sequence)
NP_001027268.1 (Protein)
NM_001032097.1 (DNA/RNA sequence)
NP_001027269.1 (Protein)
NM_001032098.1 (DNA/RNA sequence)
NP_001027270.1 (Protein)
NM_001032099.1 (DNA/RNA sequence)

KEGG enzyme name
alcohol dehydrogenase
aldehyde reductase
ADH
alcohol dehydrogenase (NAD)
aliphatic alcohol dehydrogenase
ethanol dehydrogenase
NAD-dependent alcohol dehydrogenase
NAD-specific aromatic alcohol dehydrogenase
NADH-alcohol dehydrogenase
NADH-aldehyde dehydrogenase
primary alcohol dehydrogenase
yeast alcohol dehydrogenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10807 ADH_DROLE An alcohol + NAD(+) = an aldehyde or ketone + NADH. Homodimer.
P00334 ADH_DROME An alcohol + NAD(+) = an aldehyde or ketone + NADH. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis
MAP00071 Fatty acid metabolism
MAP00120 Bile acid biosynthesis
MAP00260 Glycine, serine and threonine metabolism
MAP00350 Tyrosine metabolism
MAP00624 1- and 2-Methylnaphthalene degradation
MAP00641 3-Chloroacrylic acid degradation
MAP00830 Retinol metabolism
MAP00980 Metabolism of xenobiotics by cytochrome P450
MAP00982 Drug metabolism - cytochrome P450

Compound table
Substrates Products Intermediates
KEGG-id C00003 C00069 C00004 C00071 C00709 C00080
E.C.
Compound NAD+ Alcohol NADH Aldehyde Ketone H+
Type amide group,amine group,nucleotide carbohydrate amide group,amine group,nucleotide carbohydrate carbohydrate others
ChEBI 15846
16908
15378
PubChem 5893
439153
1038
1a4uA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1a4uB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1b14A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound Unbound
1b14B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound Unbound
1b15A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NAE (NAD-Ketone) Unbound Unbound Unbound Analogue:NAE (NAD-Ketone)
1b15B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NAE (NAD-Ketone) Unbound Unbound Unbound Analogue:NAE (NAD-Ketone)
1b16A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NAQ (NAD-Ketone) Unbound Unbound Unbound Analogue:NAQ (NAD-Ketone)
1b16B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NAQ (NAD-Ketone) Unbound Unbound Unbound Analogue:NAQ (NAD-Ketone)
1b2lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:NDC (NAD-Ketone) Unbound Unbound Unbound Analogue:NDC (NAD-Ketone)
1sbyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Analogue:ETF Unbound Unbound Unbound
1sbyB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Analogue:ETF Unbound Unbound Unbound
1mg5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound Analogue:ACT
1mg5B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:NAD Unbound Unbound Unbound Analogue:ACT

Reference for Active-site residues
resource references E.C.
PDB;1a4u & Swiss-prot;P10807

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a4uA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1a4uB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b14A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b14B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b15A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b15B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b16A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b16B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1b2lA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1sbyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1sbyB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 138;TYR 151;LYS 155
1mg5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 139;TYR 152;LYS 156
1mg5B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 139;TYR 152;LYS 156

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
Fig.5, p.3345-3346 2
[11]
p.7054
[12]
p.84
[16]
p.193
[18]
p.389-391
[20]
Fig.10, p.346-348
[21]
Fig.5, p.608-611
[25]
p.296-298
[28]
Fig.7, p.3927-3930

References
[1]
Resource
Comments
Medline ID
PubMed ID 6821373
Journal Biochem J
Year 1980
Volume 187
Pages 875-83
Authors Thatcher DR
Title The complete amino acid sequence of three alcohol dehydrogenase alleloenzymes (AdhN-11, AdhS and AdhUF) from the fruitfly Drosophila melanogaster.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6821374
Journal Biochem J
Year 1980
Volume 187
Pages 884-6
Authors Thatcher DR, Sawyer L
Title Secondary-structure prediction from the sequence of Drosophila melanogaster (fruitfly) alcohol dehydrogenase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 6789320
Journal Proc Natl Acad Sci U S A
Year 1981
Volume 78
Pages 2717-21
Authors Benyajati C, Place AR, Powers DA, Sofer W
Title Alcohol dehydrogenase gene of Drosophila melanogaster: relationship of intervening sequences to functional domains in the protein.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3160338
Journal Biochem Genet
Year 1985
Volume 23
Pages 205-16
Authors Winberg JO, Hovik R, McKinley-McKee JS
Title The alcohol dehydrogenase alleloenzymes AdhS and AdhF from the fruitfly Drosophila melanogaster: an enzymatic rate assay to determine the active-site concentration.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1804107
Journal Biochem Int
Year 1991
Volume 25
Pages 879-85
Authors McKinley-McKee JS, Winberg JO, Pettersson G
Title Mechanism of action of Drosophila melanogaster alcohol dehydrogenase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1904719
Journal Biochem J
Year 1991
Volume 276
Pages 433-8
Authors Ribas De Pouplana L, Atrian S, Gonzalex-Duarte R, Fothergill-Gilmore LA, Kelly SM, Price NC
Title Structural properties of long- and short-chain alcohol dehydrogenases. Contribution of NAD+ to stability.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1733784
Journal Int J Biochem
Year 1992
Volume 24
Pages 169-81
Authors Winberg JO, McKinley-McKee JS
Title Kinetic interpretations of active site topologies and residue exchanges in Drosophila alcohol dehydrogenases.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 1522600
Journal J Mol Biol
Year 1992
Volume 227
Pages 356-8
Authors Gordon EJ, Bury SM, Sawyer L, Atrian S, Gonzalez-Duarte R
Title Preliminary X-ray crystallographic studies on alcohol dehydrogenase from Drosophila.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 1508206
Journal Mol Cell Biol
Year 1992
Volume 12
Pages 4093-103
Authors Falb D, Maniatis T
Title Drosophila transcriptional repressor protein that binds specifically to negative control elements in fat body enhancers.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8461298
Journal Biochemistry
Year 1993
Volume 32
Pages 3342-6
Authors Chen Z, Jiang JC, Lin ZG, Lee WR, Baker ME, Chang SH
Title Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8003469
Journal Biochemistry
Year 1994
Volume 33
Pages 7047-55
Authors Ribas de Pouplana L, Fothergill-Gilmore LA
Title The active site architecture of a short-chain dehydrogenase defined by site-directed mutagenesis and structure modeling.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7988726
Journal FEBS Lett
Year 1994
Volume 356
Pages 81-5
Authors Chen Z, Tsigelny I, Lee WR, Baker ME, Chang SH
Title Adding a positive charge at residue 46 of Drosophila alcohol dehydrogenase increases cofactor specificity for NADP+.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 7772022
Journal Biochem J
Year 1995
Volume 308
Pages 419-23
Authors Chenevert SW, Fossett NG, Chang SH, Tsigelny I, Baker ME, Lee WR
Title Amino acids important in enzyme activity and dimer stability for Drosophila alcohol dehydrogenase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7588794
Journal Eur J Biochem
Year 1995
Volume 233
Pages 498-505
Authors Albalat R, Valls M, Fibla J, Atrian S, Gonzalez-Duarte R
Title Involvement of the C-terminal tail in the activity of Drosophila alcohol dehydrogenase. Evaluation of truncated proteins constructed by site-directed mutagenesis.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8547186
Journal J Steroid Biochem Mol Biol
Year 1995
Volume 55
Pages 589-600
Authors Tsigelny I, Baker ME
Title Structures important in mammalian 11 beta- and 17 beta-hydroxysteroid dehydrogenases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9280279
Journal FEBS Lett
Year 1997
Volume 413
Pages 191-3
Authors Cols N, Atrian S, Benach J, Ladenstein R, Gonzalez-Duarte R
Title Drosophila alcohol dehydrogenase: evaluation of Ser139 site-directed mutants.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9562905
Journal Biochem Genet
Year 1998
Volume 36
Pages 37-49
Authors Smilda T, Reinders P, Beintema JJ
Title Modeling studies of conformational changes in the substrate-binding loop in Drosophila alcohol dehydrogenase.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS).
Medline ID 98407982
PubMed ID 9735295
Journal J Mol Biol
Year 1998
Volume 282
Pages 383-99
Authors Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R
Title The refined crystal structure of Drosophila lebanonensis alcohol dehydrogenase at 1.9 A resolution.
Related PDB 1a4u 1b14
Related UniProtKB P10807
[19]
Resource
Comments
Medline ID
PubMed ID 9694670
Journal J Mol Evol
Year 1998
Volume 47
Pages 211-21
Authors Atrian S, Sanchez-Pulido L, Gonzalez-Duarte R, Valencia A
Title Shaping of Drosophila alcohol dehydrogenase through evolution: relationship with enzyme functionality.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
Medline ID 99296633
PubMed ID 10366509
Journal J Mol Biol
Year 1999
Volume 289
Pages 335-55
Authors Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R
Title The 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.
Related PDB 1b15 1b16 1b2l
Related UniProtKB P10807
[21]
Resource
Comments
Medline ID
PubMed ID 10610783
Journal J Mol Biol
Year 1999
Volume 294
Pages 601-16
Authors Winberg JO, Brendskag MK, Sylte I, Lindstad RI, McKinley-McKee JS
Title The catalytic triad in Drosophila alcohol dehydrogenase: pH, temperature and molecular modelling studies.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10093214
Journal J Mol Evol
Year 1999
Volume 48
Pages 262-3
Authors Atrian S, Gonzalez-Duarte R
Title The Drosophila virilis alcohol dehydrogenase catalytic residues are conserved.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10848978
Journal Eur J Biochem
Year 2000
Volume 267
Pages 3613-22
Authors Benach J, Atrian S, Fibla J, Gonzalez-Duarte R, Ladenstein R
Title Structure-function relationships in Drosophila melanogaster alcohol dehydrogenase allozymes ADH(S), ADH(F) and ADH(UF), and distantly related forms.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11443349
Journal J Mol Evol
Year 2001
Volume 52
Pages 457-66
Authors Smilda T, Kamminga AH, Reinders P, Baron W, van Hylckama Vlieg JE, Beintema JJ
Title Enzymic and structural studies on Drosophila alcohol dehydrogenase and other short-chain dehydrogenases/reductases.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12660997
Journal Proteins
Year 2003
Volume 51
Pages 289-98
Authors Koumanov A, Benach J, Atrian S, Gonzalez-Duarte R, Karshikoff A, Ladenstein R
Title The catalytic mechanism of Drosophila alcohol dehydrogenase: evidence for a proton relay modulated by the coupled ionization of the active site Lysine/Tyrosine pair and a NAD+ ribose OH switch.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 15170253
Journal J Mol Evol
Year 2004
Volume 58
Pages 493-505
Authors Eliopoulos E, Goulielmos GN, Loukas M
Title Functional constraints of alcohol dehydrogenase (ADH) of tephritidae and relationships with other Dipteran species.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 15581900
Journal J Mol Biol
Year 2005
Volume 345
Pages 579-98
Authors Benach J, Winberg JO, Svendsen JS, Atrian S, Gonzalez-Duarte R, Ladenstein R
Title Drosophila alcohol dehydrogenase: acetate-enzyme interactions and novel insights into the effects of electrostatics on catalysis.
Related PDB 1mg5
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 19011748
Journal Cell Mol Life Sci
Year 2008
Volume 65
Pages 3918-35
Authors Ladenstein R, Winberg JO, Benach J
Title Medium- and short-chain dehydrogenase/reductase gene and protein families : Structure-function relationships in short-chain alcohol dehydrogenases.
Related PDB
Related UniProtKB

Comments
(A0) Lys156 (of 1mg5) modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD, along with the N1 atom of the nicotinamide group in NAD, whereas Ser139 modulates the pKa of hydroxyl oxygen of the substrate.
(A1) Tyr152 acts as a general base to deprotonate the hydroxyl oxygen of the substrate. Meanwhile, the hydride transfer (a pro-S hydride transfer) occurs from the carbon atom with the hydroxyl group of the substrate to the C4 atom of the nicotinamide.
(B) Hydride transfer from NADH to substrate (Reduction):
(B0) Lys156 modulates the activity (or pKa) of Tyr152 via 2'-hydroxyl group of NAD(P)H, along with the N1 atom of the nicotinamide group in NADH, whereas Ser139 modulates the pKa of carbonyl oxygen of the substrate.
(B1) Tyr152 acts as a general acid to protonate the carbonyl oxygen of the substrate. Meanwhile, the hydride transfer occurs from the C4 atom of the nicotinamide to the carbonyl carbon of the substrate.
Whilst this enzyme does not utilize a zinc ion for catalysis, its counterparts (homologous enzymes) from vertebrates (such as D00018 in EzCatDB) requires zinc ion for catalysis (see [5]).
The catalytic mechanism of this enzyme must be similar to those of the homologous enzymes with the catalytic triad, Ser-Tyr-Lys (S00320, S00324, S00325, S00326, S00328, S00329, S00331, S00336 in EzCatDB).
According to the literature [20] and [28], the reaction proceeds as follows:
(A) Hydride transfer from substrate to NAD (Dehydrogenation):

Created Updated
2005-01-06 2011-06-22