ADH1_ARTAN
ID ADH1_ARTAN Reviewed; 378 AA.
AC A0A2U1Q018; G8EHE1;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Alcohol dehydrogenase 1 {ECO:0000303|PubMed:23575629};
DE EC=1.1.1.- {ECO:0000269|PubMed:23575629};
DE AltName: Full=Artemisinic aldehyde synthase {ECO:0000305|PubMed:23575629};
GN Name=ADH1 {ECO:0000303|PubMed:23575629};
GN ORFNames=CTI12_AA090660 {ECO:0000312|EMBL:PWA91359.1};
OS Artemisia annua (Sweet wormwood).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Artemisiinae; Artemisia.
OX NCBI_TaxID=35608;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, BIOTECHNOLOGY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Trichome gland;
RX PubMed=23575629; DOI=10.1038/nature12051;
RA Paddon C.J., Westfall P.J., Pitera D.J., Benjamin K., Fisher K., McPhee D.,
RA Leavell M.D., Tai A., Main A., Eng D., Polichuk D.R., Teoh K.H., Reed D.W.,
RA Treynor T., Lenihan J., Fleck M., Bajad S., Dang G., Diola D., Dorin G.,
RA Ellens K.W., Fickes S., Galazzo J., Gaucher S.P., Geistlinger T., Henry R.,
RA Hepp M., Horning T., Iqbal T., Jiang H., Kizer L., Lieu B., Melis D.,
RA Moss N., Regentin R., Secrest S., Tsuruta H., Vazquez R., Westblade L.F.,
RA Xu L., Yu M., Zhang Y., Zhao L., Lievense J., Covello P.S., Keasling J.D.,
RA Reiling K.K., Renninger N.S., Newman J.D.;
RT "High-level semi-synthetic production of the potent antimalarial
RT artemisinin.";
RL Nature 496:528-532(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Huhao1; TISSUE=Leaf;
RX PubMed=29703587; DOI=10.1016/j.molp.2018.03.015;
RA Shen Q., Zhang L., Liao Z., Wang S., Yan T., Shi P., Liu M., Fu X., Pan Q.,
RA Wang Y., Lv Z., Lu X., Zhang F., Jiang W., Ma Y., Chen M., Hao X., Li L.,
RA Tang Y., Lv G., Zhou Y., Sun X., Brodelius P.E., Rose J.K.C., Tang K.;
RT "The genome of Artemisia annua provides insight into the evolution of
RT Asteraceae family and artemisinin biosynthesis.";
RL Mol. Plant 11:776-788(2018).
RN [3]
RP REVIEW ON ARTEMISININ ANTIMALARIAL PROPERTIES.
RX PubMed=27488942; DOI=10.1002/anie.201601967;
RA Tu Y.;
RT "Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel
RT Lecture).";
RL Angew. Chem. Int. Ed. 55:10210-10226(2016).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=30851440; DOI=10.1016/j.molp.2019.02.011;
RA Judd R., Bagley M.C., Li M., Zhu Y., Lei C., Yuzuak S., Ekeloef M., Pu G.,
RA Zhao X., Muddiman D.C., Xie D.-Y.;
RT "Artemisinin biosynthesis in non-glandular trichome cells of Artemisia
RT annua.";
RL Mol. Plant 12:704-714(2019).
RN [5]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=32514287; DOI=10.1186/s13020-020-00336-8;
RA Uzun T., Toptas O.;
RT "Artesunate: could be an alternative drug to chloroquine in COVID-19
RT treatment?";
RL Chin. Med. J. 15:54-54(2020).
RN [7]
RP BIOTECHNOLOGY, AND REVIEW.
RX PubMed=32405226; DOI=10.1016/j.phrs.2020.104901;
RA Cheong D.H.J., Tan D.W.S., Wong F.W.S., Tran T.;
RT "Anti-malarial drug, artemisinin and its derivatives for the treatment of
RT respiratory diseases.";
RL Pharmacol. Res. 158:104901-104901(2020).
CC -!- FUNCTION: Involved in the biosynthesis of the antimalarial endoperoxide
CC artemisinin (PubMed:23575629, PubMed:27488942). Catalyzes the
CC conversion of artemisinic alcohol into artemisinic aldehyde
CC (PubMed:23575629). {ECO:0000269|PubMed:23575629,
CC ECO:0000303|PubMed:27488942}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-artemisinic alcohol + NAD(+) = (+)-artemisinic aldehyde +
CC H(+) + NADH; Xref=Rhea:RHEA:60712, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:64688,
CC ChEBI:CHEBI:64783; Evidence={ECO:0000269|PubMed:23575629};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60713;
CC Evidence={ECO:0000269|PubMed:23575629};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P40394};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for artemisinic alcohol {ECO:0000269|PubMed:23575629};
CC Note=kcat is 41 sec(-1) with artemisinic alcohol as substrate.
CC {ECO:0000269|PubMed:23575629};
CC -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000303|PubMed:30468448}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P40394}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:W8JWV8}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:W8JWV8}.
CC -!- TISSUE SPECIFICITY: Present in non-glandular trichome cells.
CC {ECO:0000269|PubMed:30851440}.
CC -!- BIOTECHNOLOGY: Artemisinin and derivatives (e.g. artesunate), are
CC antimalarial drugs due to their endoperoxidase properties; they also
CC display multiple pharmacological actions against inflammation,viral
CC infections, and cell and tumor proliferation (PubMed:32514287,
CC PubMed:32405226). Artesunate may be a promising treatment for COVID-19
CC mediated by the severe acute respiratory syndrome coronavirus 2 (2019-
CC nCoV) (SARS-CoV-2) because of its anti-inflammatory activity, NF-kappaB
CC (nuclear factor kappa B)-coronavirus effect and chloroquine-like
CC endocytosis inhibition mechanism (PubMed:32514287, PubMed:32405226).
CC {ECO:0000303|PubMed:32405226, ECO:0000303|PubMed:32514287}.
CC -!- BIOTECHNOLOGY: Yeast (S.cerevisiae) has been engineered to produce
CC artemisinic-acid, a precursor of the antimalarial artemisinin compound,
CC by expressing AMS1/ADS, CYP71AV1, ADH1 and ALDH1 in conjunction with
CC CYB5 and CPR1. {ECO:0000269|PubMed:23575629}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Class-IV subfamily. {ECO:0000305}.
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DR EMBL; JF910157; AEI16475.1; -; mRNA.
DR EMBL; PKPP01000550; PWA91359.1; -; Genomic_DNA.
DR PDB; 6LJH; X-ray; 1.80 A; A=1-378.
DR PDB; 7CYI; X-ray; 2.95 A; A/B/C/D=1-378.
DR PDBsum; 6LJH; -.
DR PDBsum; 7CYI; -.
DR AlphaFoldDB; A0A2U1Q018; -.
DR SMR; A0A2U1Q018; -.
DR STRING; 35608.A0A2U1Q018; -.
DR Proteomes; UP000245207; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071704; P:organic substance metabolic process; IEA:UniProt.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
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 PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; NAD; Nucleus; Oxidoreductase;
KW Reference proteome; Zinc.
FT CHAIN 1..378
FT /note="Alcohol dehydrogenase 1"
FT /id="PRO_0000447845"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 49..53
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 202..207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 226
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 274..276
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 297..299
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT BINDING 321..323
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P40394"
FT CONFLICT 19..20
FT /note="LG -> SS (in Ref. 1; AEI16475)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="V -> I (in Ref. 1; AEI16475)"
FT /evidence="ECO:0000305"
FT STRAND 9..16
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 23..30
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 37..45
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 49..55
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:6LJH"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:7CYI"
FT STRAND 149..156
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 178..188
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 205..216
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 254..260
FT /evidence="ECO:0007829|PDB:6LJH"
FT TURN 261..264
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 277..286
FT /evidence="ECO:0007829|PDB:6LJH"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:7CYI"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:7CYI"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:6LJH"
FT TURN 328..331
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 332..340
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 350..355
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:6LJH"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:6LJH"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:6LJH"
SQ SEQUENCE 378 AA; 40397 MW; 2BEBE6C742B2E0BB CRC64;
MAQKAPGVIT CKAAVVWELG GPVVLEEIRV DPPKASEVRI KMLCASLCHT DVLCTKGFPI
PLFPRIPGHE GVGVIESVGK DAKGLKPGDI VMPLYLGECG QCLNCKTGKT NLCHVYPPSF
SGLMNDGTSR MSIARTGESI YHFASCSTWT EYAVADCNYV LKINPKISYP HASFLSCGFT
TGFGATWRET QVSKGSSVAV FGIGTVGLGV IKGAQLQGAS KIIGVDVNQY KAAKGKVFGM
TDFINPKDHP DKSVSELVKE LTHGLGVDHC FECTGVPSLL NEALEASKIG IGTVVPIGAG
GEASVAINSL ILFSGRTLKF TAFGGVRTQS DLPVIIDKCL NKEIQLDELL THEIHLDNIQ
EAFEILKKPD CVKILIKF
