LAD_ASPNC
ID LAD_ASPNC Reviewed; 386 AA.
AC A2QAC0; Q5GN52;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=L-arabinitol 4-dehydrogenase;
DE Short=LAD;
DE EC=1.1.1.12;
GN Name=ladA; ORFNames=An01g10920;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RA de Groot M.J.L., Vandeputte-Rutten L., van den Dool C., Woesten H.A.B.,
RA Levisson M., vanKuyk P.A., Ruijter G.J.G., de Vries R.P.;
RT "Diversity in regulation and substrate specificity of the pentose catabolic
RT pathway genes/enzymes of Aspergillus niger.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [3]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=16321042; DOI=10.1021/bp050189o;
RA de Groot M.J., Prathumpai W., Visser J., Ruijter G.J.;
RT "Metabolic control analysis of Aspergillus niger L-arabinose catabolism.";
RL Biotechnol. Prog. 21:1610-1616(2005).
RN [4]
RP FUNCTION, MUTAGENESIS OF MET-70 AND TYR-318, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19674460; DOI=10.1186/1471-2180-9-166;
RA Rutten L., Ribot C., Trejo-Aguilar B., Wosten H.A., de Vries R.P.;
RT "A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA)
RT from Aspergillus niger results in a significant increase in affinity for D-
RT sorbitol.";
RL BMC Microbiol. 9:166-166(2009).
RN [5]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, MUTAGENESIS OF
RP 213-ASP-ILE-214 AND ALA-359, AND ZINC-BINDING.
RX PubMed=20414651; DOI=10.1007/s00253-010-2593-4;
RA Kim B., Sullivan R.P., Zhao H.;
RT "Cloning, characterization, and engineering of fungal L-arabinitol
RT dehydrogenases.";
RL Appl. Microbiol. Biotechnol. 87:1407-1414(2010).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of L-arabinitol to L-
CC xylulose in the fungal L-arabinose catabolic pathway. L-arabinose
CC catabolism is important for using plant material as a carbon source.
CC Not active with NADP as cosubstrate. {ECO:0000269|PubMed:19674460,
CC ECO:0000269|PubMed:20414651}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arabinitol + NAD(+) = H(+) + L-xylulose + NADH;
CC Xref=Rhea:RHEA:16381, ChEBI:CHEBI:15378, ChEBI:CHEBI:17399,
CC ChEBI:CHEBI:18403, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.12;
CC Evidence={ECO:0000269|PubMed:16321042};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20414651};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:20414651};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=89 mM for L-arabinitol (at pH 9.6) {ECO:0000269|PubMed:16321042,
CC ECO:0000269|PubMed:19674460, ECO:0000269|PubMed:20414651};
CC KM=5 mM for L-xylulose (at pH 9.6) {ECO:0000269|PubMed:16321042,
CC ECO:0000269|PubMed:19674460, ECO:0000269|PubMed:20414651};
CC KM=50 uM for NAD (at pH 9.6) {ECO:0000269|PubMed:16321042,
CC ECO:0000269|PubMed:19674460, ECO:0000269|PubMed:20414651};
CC KM=8 uM for NADH (at pH 9.6) {ECO:0000269|PubMed:16321042,
CC ECO:0000269|PubMed:19674460, ECO:0000269|PubMed:20414651};
CC Vmax=96 umol/min/mg enzyme for the forward reaction
CC {ECO:0000269|PubMed:16321042, ECO:0000269|PubMed:19674460,
CC ECO:0000269|PubMed:20414651};
CC Vmax=805 umol/min/mg enzyme for the reverse reaction
CC {ECO:0000269|PubMed:16321042, ECO:0000269|PubMed:19674460,
CC ECO:0000269|PubMed:20414651};
CC pH dependence:
CC Optimum pH is 9.4. Active from pH 7 to pH 11.
CC {ECO:0000269|PubMed:16321042, ECO:0000269|PubMed:19674460,
CC ECO:0000269|PubMed:20414651};
CC Temperature dependence:
CC Optimum temperature is 40-50 degrees Celsius.
CC {ECO:0000269|PubMed:16321042, ECO:0000269|PubMed:19674460,
CC ECO:0000269|PubMed:20414651};
CC -!- PATHWAY: Carbohydrate degradation; L-arabinose degradation via L-
CC arabinitol; D-xylulose 5-phosphate from L-arabinose (fungal route):
CC step 2/5. {ECO:0000269|PubMed:16321042}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:20414651}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; AJ854040; CAH69383.1; -; Genomic_DNA.
DR EMBL; AM269980; CAK37272.1; -; Genomic_DNA.
DR RefSeq; XP_001389509.1; XM_001389472.2.
DR AlphaFoldDB; A2QAC0; -.
DR SMR; A2QAC0; -.
DR PaxDb; A2QAC0; -.
DR EnsemblFungi; CAK37272; CAK37272; An01g10920.
DR GeneID; 4977395; -.
DR KEGG; ang:ANI_1_1474014; -.
DR VEuPathDB; FungiDB:An01g10920; -.
DR HOGENOM; CLU_026673_11_5_1; -.
DR BioCyc; MetaCyc:MON-13195; -.
DR BRENDA; 1.1.1.12; 518.
DR UniPathway; UPA00146; UER00575.
DR Proteomes; UP000006706; Chromosome 2R.
DR GO; GO:0050019; F:L-arabinitol 4-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0019569; P:L-arabinose catabolic process to xylulose 5-phosphate; IEA:UniProtKB-UniPathway.
DR CDD; cd05285; sorbitol_DH; 1.
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; IPR045306; SDH-like.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW Arabinose catabolism; Carbohydrate metabolism; Metal-binding; NAD;
KW Oxidoreductase; Reference proteome; Zinc.
FT CHAIN 1..386
FT /note="L-arabinitol 4-dehydrogenase"
FT /id="PRO_0000418404"
FT BINDING 55
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 192..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 218
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 317..319
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MUTAGEN 70
FT /note="M->F: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:19674460"
FT MUTAGEN 213..214
FT /note="DI->SR: Alters cofactor specificity from NAD to
FT NADP; when associated with T-359."
FT /evidence="ECO:0000269|PubMed:20414651"
FT MUTAGEN 318
FT /note="Y->F: Increases affinity for D-sorbitol."
FT /evidence="ECO:0000269|PubMed:19674460"
FT MUTAGEN 359
FT /note="A->T: Alters cofactor specificity from NAD to NADP;
FT when associated with 213-SR-214."
FT /evidence="ECO:0000269|PubMed:20414651"
SQ SEQUENCE 386 AA; 41345 MW; CCC018D7E5CF75C6 CRC64;
MATATVLEKA NIGVFTNTKH DLWVADAKPT LEEVKNGQGL QPGEVTIEVR STGICGSDVH
FWHAGCIGPM IVTGDHILGH ESAGQVVAVA PDVTSLKPGD RVAVEPNIIC NACEPCLTGR
YNGCENVQFL STPPVDGLLR RYVNHPAIWC HKIGDMSYED GALLEPLSVS LAGIERSGLR
LGDPCLVTGA GPIGLITLLS ARAAGASPIV ITDIDEGRLE FAKSLVPDVR TYKVQIGLSA
EQNAEGIINV FNDGQGSGPG ALRPRIAMEC TGVESSVASA IWSVKFGGKV FVIGVGKNEM
TVPFMRLSTW EIDLQYQYRY CNTWPRAIRL VRNGVIDLKK LVTHRFLLED AIKAFETAAN
PKTGAIKVQI MSSEDDVKAA SAGQKI
