LAD_HYPJE
ID LAD_HYPJE Reviewed; 377 AA.
AC Q96V44;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=L-arabinitol 4-dehydrogenase;
DE Short=LAD;
DE EC=1.1.1.12;
GN Name=lad1;
OS Hypocrea jecorina (Trichoderma reesei).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=51453;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 12-40;
RP 323-329 AND 357-365, FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 56765 / Rut C-30;
RX PubMed=11514550; DOI=10.1074/jbc.m104022200;
RA Richard P., Londesborough J., Putkonen M., Kalkkinen N., Penttila M.;
RT "Cloning and expression of a fungal L-arabinitol 4-dehydrogenase gene.";
RL J. Biol. Chem. 276:40631-40637(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 26921 / CBS 392.92 / QM9414;
RX PubMed=14555469; DOI=10.1128/ec.2.5.867-875.2003;
RA Seiboth B., Hartl L., Pail M., Kubicek C.P.;
RT "D-xylose metabolism in Hypocrea jecorina: loss of the xylitol
RT dehydrogenase step can be partially compensated for by lad1-encoded L-
RT arabinitol-4-dehydrogenase.";
RL Eukaryot. Cell 2:867-875(2003).
RN [3]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15128296; DOI=10.1111/j.1432-1033.2004.04088.x;
RA Pail M., Peterbauer T., Seiboth B., Hametner C., Druzhinina I.,
RA Kubicek C.P.;
RT "The metabolic role and evolution of L-arabinitol 4-dehydrogenase of
RT Hypocrea jecorina.";
RL Eur. J. Biochem. 271:1864-1872(2004).
RN [4]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, MUTAGENESIS OF
RP 224-ASP-ILE-225 AND ALA-362, 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 Can partially compensate for xylitol dehydrogenase in xdh1 mutants.
CC Also oxidizes galactitol to L-xylo-3-hexulose as an alternative to the
CC standard Leloir pathway for D-galactose metabolism. NADP cannot act as
CC a cosubstrate. {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:14555469, ECO:0000269|PubMed:15128296,
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:11514550};
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=18 mM for L-arabinitol (at pH 7) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=200 mM for xylitol (at pH 7) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=4.5 mM for L-arabinitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=25 mM for D-talitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=60 mM for galactitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=46 mM for D-sorbitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=11.3 mM for D-allitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=37 mM for L-mannitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=191 mM for L-iditol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=580 mM for D-arabino-3-hexulose (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC KM=81 mM for L-xylo-3-hexulose (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC KM=96 mM for D-fructose (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=81 mM for D-psicose (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=19 mM for L-sorbitol (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=28 mM for L-tagatose (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=115 mM for D-sorbose (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC KM=180 uM for NAD (at pH 7) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC Vmax=27 nmol/sec/mg enzyme with L-arabinitol as substrate (at pH 9
CC and 10) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=10 nmol/sec/mg enzyme with L-arabinitol as substrate (at pH 7)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=6 nmol/sec/mg enzyme with xylitol as substrate (at pH 7)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.213 nmol/sec/mg enzyme with L-arabinitol as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.146 nmol/sec/mg enzyme with D-talitol as substrate (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.012 nmol/sec/mg enzyme with galactitol as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.034 nmol/sec/mg enzyme with D-sorbitol as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.008 nmol/sec/mg enzyme with D-allitol as substrate (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.027 nmol/sec/mg enzyme with L-mannitol as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.021 nmol/sec/mg enzyme with L-iditol as substrate (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.969 nmol/sec/mg enzyme with D-arabino-3-hexulose as substrate
CC (at pH 8.6) {ECO:0000269|PubMed:11514550,
CC ECO:0000269|PubMed:15128296, ECO:0000269|PubMed:20414651};
CC Vmax=0.197 nmol/sec/mg enzyme with L-xylo-3-hexulose as substrate (at
CC pH 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.008 nmol/sec/mg enzyme with D-fructose as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.011 nmol/sec/mg enzyme with D-psicose as substrate (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.001 nmol/sec/mg enzyme with L-sorbitol as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.003 nmol/sec/mg enzyme with L-tagatose as substrate (at pH
CC 8.6) {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Vmax=0.001 nmol/sec/mg enzyme with D-sorbose as substrate (at pH 8.6)
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
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:11514550, ECO:0000269|PubMed:15128296,
CC ECO:0000269|PubMed:20414651};
CC Temperature dependence:
CC Optimum temperature is 55-65 degrees Celsius.
CC {ECO:0000269|PubMed:11514550, ECO:0000269|PubMed:15128296,
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.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:20414651}.
CC -!- INDUCTION: Only expressed when grown on L-arabinose.
CC {ECO:0000269|PubMed:11514550}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; AF355628; AAL08944.1; -; mRNA.
DR EMBL; AY225444; AAP57209.1; -; Genomic_DNA.
DR AlphaFoldDB; Q96V44; -.
DR SMR; Q96V44; -.
DR VEuPathDB; FungiDB:TrQ_003398; -.
DR OMA; VGKNEMT; -.
DR BioCyc; MetaCyc:MON-13196; -.
DR BRENDA; 1.1.1.12; 6451.
DR SABIO-RK; Q96V44; -.
DR UniPathway; UPA00146; UER00575.
DR GO; GO:0050019; F:L-arabinitol 4-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019568; P:arabinose catabolic process; IMP:UniProtKB.
DR GO; GO:0042843; P:D-xylose catabolic process; IMP:UniProtKB.
DR GO; GO:0019388; P:galactose catabolic process; IMP:UniProtKB.
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; 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.
PE 1: Evidence at protein level;
KW Arabinose catabolism; Carbohydrate metabolism; Direct protein sequencing;
KW Galactose metabolism; Metal-binding; NAD; Oxidoreductase;
KW Xylose metabolism; Zinc.
FT CHAIN 1..377
FT /note="L-arabinitol 4-dehydrogenase"
FT /id="PRO_0000418403"
FT BINDING 66
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="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 121
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 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 203..204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 320..322
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MUTAGEN 224..225
FT /note="DI->SR: Alters cofactor specificity from NAD to
FT NADP; when associated with T-362."
FT /evidence="ECO:0000269|PubMed:20414651"
FT MUTAGEN 362
FT /note="A->T: Alters cofactor specificity from NAD to NADP;
FT when associated with 224-SR-225."
FT /evidence="ECO:0000269|PubMed:20414651"
SQ SEQUENCE 377 AA; 39886 MW; 5015D4A61D948D1D CRC64;
MSPSAVDDAP KATGAAISVK PNIGVFTNPK HDLWISEAEP SADAVKSGAD LKPGEVTIAV
RSTGICGSDV HFWHAGCIGP MIVEGDHILG HESAGEVIAV HPTVSSLQIG DRVAIEPNII
CNACEPCLTG RYNGCEKVEF LSTPPVPGLL RRYVNHPAVW CHKIGNMSWE NGALLEPLSV
ALAGMQRAKV QLGDPVLVCG AGPIGLVSML CAAAAGACPL VITDISESRL AFAKEICPRV
TTHRIEIGKS AEETAKSIVS SFGGVEPAVT LECTGVESSI AAAIWASKFG GKVFVIGVGK
NEISIPFMRA SVREVDIQLQ YRYSNTWPRA IRLIESGVID LSKFVTHRFP LEDAVKAFET
SADPKSGAIK VMIQSLD
