ADHN_AMYME
ID ADHN_AMYME Reviewed; 371 AA.
AC P80175;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=NDMA-dependent alcohol dehydrogenase {ECO:0000303|PubMed:8385013};
DE Short=NDMA-ADH {ECO:0000303|PubMed:8385013};
DE EC=1.1.99.36 {ECO:0000269|PubMed:8385013};
DE AltName: Full=Nicotinoprotein alcohol/aldehyde oxidoreductase {ECO:0000303|PubMed:8385013};
OS Amycolatopsis methanolica.
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis; Amycolatopsis methanolica group.
OX NCBI_TaxID=1814;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=12827287; DOI=10.1007/s00018-003-3105-9;
RA Norin A., Piersma S.R., Duine J.A., Jornvall H.;
RT "Nicotinoprotein (NAD+ -containing) alcohol dehydrogenase: structural
RT relationships and functional interpretations.";
RL Cell. Mol. Life Sci. 60:999-1006(2003).
RN [2]
RP PROTEIN SEQUENCE OF 1-41, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=DSM 44096 / JCM 8087 / NBRC 15065 / NCIMB 11946 / NRRL B-24139 / LMD
RC 80.32 / 239;
RX PubMed=8385013; DOI=10.1111/j.1432-1033.1993.tb17723.x;
RA van Ophem P.W., van Beeumen J., Duine J.A.;
RT "Nicotinoprotein [NAD(P)-containing] alcohol/aldehyde oxidoreductases.
RT Purification and characterization of a novel type from Amycolatopsis
RT methanolica.";
RL Eur. J. Biochem. 212:819-826(1993).
RN [3]
RP ACTIVITY REGULATION.
RX PubMed=9485460; DOI=10.1021/bi972115u;
RA Piersma S.R., Visser A.J., de Vries S., Duine J.A.;
RT "Optical spectroscopy of nicotinoprotein alcohol dehydrogenase from
RT Amycolatopsis methanolica: a comparison with horse liver alcohol
RT dehydrogenase and UDP-galactose epimerase.";
RL Biochemistry 37:3068-3077(1998).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=14690248; DOI=10.1023/b:jopc.0000005461.53788.ee;
RA Piersma S.R., Norin A., de Vries S., Jornvall H., Duine J.A.;
RT "Inhibition of nicotinoprotein (NAD+-containing) alcohol dehydrogenase by
RT trans-4-(N,N-dimethylamino)-cinnamaldehyde binding to the active site.";
RL J. Protein Chem. 22:457-461(2003).
CC -!- FUNCTION: Catalytically different from common alcohol dehydrogenases.
CC Effective in oxidizing ethanol, other primary alcohols and
CC benzylalcohol only in the presence of p-nitroso-N,N-dimethylaniline
CC (NDMA) as an electron acceptor. NADH acts as a cofactor here instead as
CC a coenzyme. {ECO:0000269|PubMed:8385013}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a primary alcohol + N,N-dimethyl-4-nitrosoaniline = 4-
CC (hydroxylamino)-N,N-dimethylaniline + an aldehyde;
CC Xref=Rhea:RHEA:48076, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478,
CC ChEBI:CHEBI:59990, ChEBI:CHEBI:59991;
CC Evidence={ECO:0000269|PubMed:8385013};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + ethanol = acetaldehyde + AH2; Xref=Rhea:RHEA:33567,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15343, ChEBI:CHEBI:16236,
CC ChEBI:CHEBI:17499; EC=1.1.99.36;
CC Evidence={ECO:0000269|PubMed:8385013};
CC -!- COFACTOR:
CC Name=NADH; Xref=ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:8385013};
CC -!- ACTIVITY REGULATION: Inhibited by trans-4-(N,N-dimethylamino)-
CC cinnamaldehyde through direct binding to the catalytic zinc ion in a
CC substrate-like geometry. Isobutyramide acts as competitive inhibitor
CC with respect to the electron acceptor NDMA. Acetaldehyde, AMP, ADP,
CC ATP, as well as CuSO(4), FeSO(4), HgCl(2), NiCl(2), ZnSO(4), KCN, and
CC NaN(3) are additional inhibitors of the catalytic activity.
CC {ECO:0000269|PubMed:14690248, ECO:0000269|PubMed:8385013,
CC ECO:0000269|PubMed:9485460}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.082 mM for ethanol {ECO:0000269|PubMed:8385013};
CC KM=0.0039 mM for 1-propanol {ECO:0000269|PubMed:8385013};
CC KM=0.0025 mM for 1-butanol {ECO:0000269|PubMed:8385013};
CC KM=13.4 mM for 2-propanol {ECO:0000269|PubMed:8385013};
CC KM=10.1 mM for 2-butanol {ECO:0000269|PubMed:8385013};
CC KM=6.0 mM for formaldehyde {ECO:0000269|PubMed:8385013};
CC Vmax=5.9 umol/min/mg enzyme toward ethanol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=6.09 umol/min/mg enzyme toward 1-propanol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=6.09 umol/min/mg enzyme toward 1-butanol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=5.94 umol/min/mg enzyme toward 2-propanol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=5.7 umol/min/mg enzyme toward 2-butanol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=5.7 umol/min/mg enzyme toward benzylalcohol
CC {ECO:0000269|PubMed:8385013};
CC Vmax=4.96 umol/min/mg enzyme toward formaldehyde
CC {ECO:0000269|PubMed:8385013};
CC Note=KM for benzylalcohol is lower than 0.005 mM.
CC {ECO:0000269|PubMed:8385013};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:8385013};
CC Temperature dependence:
CC Optimum temperature is 45 degrees Celsius.
CC {ECO:0000269|PubMed:8385013};
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:8385013}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR PIR; S30335; S30335.
DR AlphaFoldDB; P80175; -.
DR SMR; P80175; -.
DR BioCyc; MetaCyc:MON-15638; -.
DR BRENDA; 1.1.99.36; 314.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR023921; ADH_Zn_actinomycetes.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR03989; Rxyl_3153; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Metal-binding; NAD; Oxidoreductase; Zinc.
FT CHAIN 1..371
FT /note="NDMA-dependent alcohol dehydrogenase"
FT /id="PRO_0000064453"
FT BINDING 40
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 61
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
SQ SEQUENCE 371 AA; 38992 MW; A3BC614F4A410C23 CRC64;
MKTKAAVLHS AGKPFEIEEL ELDGPREGEV LIKYTAAGLC HSDLHLIDND LVPRFPIVGG
HEGAGVIEDV GPGVTKVKPG DHVVCSFIPN CGTCRYCATG RSNLCDMGAT ILDGGMPDGS
FRFHRGGTDY GAMCMLGTFS ERATISQHSV VKVDDWLPLE TAVLVGCGVP TGWASANYAG
GVRAGDTCVV YGIGGIGINA VQGAAHAGAA NVIAVDPVAF KREKALELGA THAFASADEA
AAKVAELTWG QMADQALITV GTVVEQVVTD AFNVIGKGGT VVITGLANPE KLTVHLSGGV
MTLFEKTVKG TLFGSANPQY DIVRLLRLYQ AGHVKLDELV TKRYSLEEVN EGYQDLRDGK
NIRGVIMHSA D
