LAD_NEUCR
ID LAD_NEUCR Reviewed; 363 AA.
AC Q7SI09;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=L-arabinitol 4-dehydrogenase;
DE Short=LAD;
DE EC=1.1.1.12;
GN Name=ard-1; ORFNames=NCU00643;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MUTAGENESIS OF PHE-59, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17938906; DOI=10.1007/s00253-007-1225-0;
RA Sullivan R., Zhao H.;
RT "Cloning, characterization, and mutational analysis of a highly active and
RT stable L-arabinitol 4-dehydrogenase from Neurospora crassa.";
RL Appl. Microbiol. Biotechnol. 77:845-852(2007).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC,
RP MUTAGENESIS OF 211-ASP-ILE-212 AND SER-348, COFACTOR, AND SUBUNIT.
RX PubMed=20655316; DOI=10.1016/j.jmb.2010.07.033;
RA Bae B., Sullivan R.P., Zhao H., Nair S.K.;
RT "Structure and engineering of L-arabinitol 4-dehydrogenase from Neurospora
RT crassa.";
RL J. Mol. Biol. 402:230-240(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 on D-arabinitol, D-sorbitol and D-mannitol.
CC {ECO:0000269|PubMed:17938906}.
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:17938906};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:17938906, ECO:0000269|PubMed:20655316};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:17938906,
CC ECO:0000269|PubMed:20655316};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 mM for L-arabinitol (at pH 8) {ECO:0000269|PubMed:17938906};
CC KM=290 mM for xylitol (at pH 8) {ECO:0000269|PubMed:17938906};
CC KM=35 mM for adonitol (at pH 8) {ECO:0000269|PubMed:17938906};
CC KM=174 uM for NAD (at pH 8) {ECO:0000269|PubMed:17938906};
CC pH dependence:
CC Optimum pH is 9.5. Active from pH 8 to pH 10.5.
CC {ECO:0000269|PubMed:17938906};
CC Temperature dependence:
CC Optimum temperature is 45-55 degrees Celsius.
CC {ECO:0000269|PubMed:17938906};
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:17938906,
CC ECO:0000269|PubMed:20655316}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; CM002236; EAA36547.1; -; Genomic_DNA.
DR RefSeq; XP_965783.1; XM_960690.2.
DR PDB; 3M6I; X-ray; 2.60 A; A/B=1-363.
DR PDBsum; 3M6I; -.
DR AlphaFoldDB; Q7SI09; -.
DR SMR; Q7SI09; -.
DR STRING; 5141.EFNCRP00000000635; -.
DR EnsemblFungi; EAA36547; EAA36547; NCU00643.
DR GeneID; 3881980; -.
DR KEGG; ncr:NCU00643; -.
DR VEuPathDB; FungiDB:NCU00643; -.
DR HOGENOM; CLU_026673_11_5_1; -.
DR InParanoid; Q7SI09; -.
DR BRENDA; 1.1.1.12; 3627.
DR UniPathway; UPA00146; UER00575.
DR Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR GO; GO:0050019; F:L-arabinitol 4-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0003939; F:L-iditol 2-dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0019569; P:L-arabinose catabolic process to xylulose 5-phosphate; IEA:UniProtKB-UniPathway.
DR GO; GO:0006062; P:sorbitol catabolic process; IBA:GO_Central.
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 3D-structure; Arabinose catabolism; Carbohydrate metabolism; Metal-binding;
KW NAD; Nucleotide-binding; Oxidoreductase; Reference proteome; Zinc.
FT CHAIN 1..363
FT /note="L-arabinitol 4-dehydrogenase"
FT /id="PRO_0000418405"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 78
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="structural"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 190..191
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 211
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 216
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 282
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:20655316"
FT BINDING 306..308
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:20655316"
FT MUTAGEN 59
FT /note="F->A,S,Y: No effect."
FT /evidence="ECO:0000269|PubMed:17938906"
FT MUTAGEN 211..212
FT /note="DI->SR: Alters cofactor specificity from NAD to
FT NADP; when associated with T-348."
FT /evidence="ECO:0000269|PubMed:20655316"
FT MUTAGEN 348
FT /note="S->T: Alters cofactor specificity from NAD to NADP;
FT when associated with 211-SR-212."
FT /evidence="ECO:0000269|PubMed:20655316"
FT STRAND 10..14
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 20..24
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 29..34
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 42..51
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 54..62
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 156..175
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 190..201
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 214..223
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 293..299
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 313..321
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 331..336
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 340..348
FT /evidence="ECO:0007829|PDB:3M6I"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:3M6I"
FT STRAND 355..360
FT /evidence="ECO:0007829|PDB:3M6I"
SQ SEQUENCE 363 AA; 39136 MW; 6A1CDDDB24D2AE40 CRC64;
MASSASKTNI GVFTNPQHDL WISEASPSLE SVQKGEELKE GEVTVAVRST GICGSDVHFW
KHGCIGPMIV ECDHVLGHES AGEVIAVHPS VKSIKVGDRV AIEPQVICNA CEPCLTGRYN
GCERVDFLST PPVPGLLRRY VNHPAVWCHK IGNMSYENGA MLEPLSVALA GLQRAGVRLG
DPVLICGAGP IGLITMLCAK AAGACPLVIT DIDEGRLKFA KEICPEVVTH KVERLSAEES
AKKIVESFGG IEPAVALECT GVESSIAAAI WAVKFGGKVF VIGVGKNEIQ IPFMRASVRE
VDLQFQYRYC NTWPRAIRLV ENGLVDLTRL VTHRFPLEDA LKAFETASDP KTGAIKVQIQ
SLE
