DHSO_SHEEP
ID DHSO_SHEEP Reviewed; 354 AA.
AC P07846;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Sorbitol dehydrogenase {ECO:0000303|PubMed:1459146, ECO:0000303|PubMed:6705798};
DE Short=SDH {ECO:0000303|PubMed:1459146};
DE EC=1.1.1.- {ECO:0000269|PubMed:1459146};
DE AltName: Full=L-iditol 2-dehydrogenase {ECO:0000305|PubMed:1459146};
DE EC=1.1.1.14 {ECO:0000269|PubMed:1459146};
DE AltName: Full=Polyol dehydrogenase {ECO:0000305};
DE AltName: Full=Xylitol dehydrogenase {ECO:0000305|PubMed:1459146};
DE Short=XDH;
DE EC=1.1.1.9 {ECO:0000269|PubMed:1459146};
GN Name=SORD;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=6705798; DOI=10.1111/j.1432-1033.1984.tb08059.x;
RA Jeffery J., Cederlund E., Joernvall H.;
RT "Sorbitol dehydrogenase. The primary structure of the sheep-liver enzyme.";
RL Eur. J. Biochem. 140:7-16(1984).
RN [2]
RP SIMILARITY TO ZINC ALCOHOL DEHYDROGENASES.
RX PubMed=6368230; DOI=10.1111/j.1432-1033.1984.tb08061.x;
RA Joernvall H., von Bahr-Lindstroem H., Jeffery J.;
RT "Extensive variations and basic features in the alcohol dehydrogenase-
RT sorbitol dehydrogenase family.";
RL Eur. J. Biochem. 140:17-23(1984).
RN [3]
RP 3D-STRUCTURE MODELING.
RX PubMed=2936393; DOI=10.1021/bi00348a025;
RA Eklund H., Horjales E., Joernvall H., Branden C.I., Jeffery J.;
RT "Molecular aspects of functional differences between alcohol and sorbitol
RT dehydrogenases.";
RL Biochemistry 24:8005-8012(1985).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=1459146; DOI=10.1111/j.1432-1033.1992.tb17465.x;
RA Lindstad R.I., Hermansen L.F., McKinley-McKee J.S.;
RT "The kinetic mechanism of sheep liver sorbitol dehydrogenase.";
RL Eur. J. Biochem. 210:641-647(1992).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND
RP ZINC, COFACTOR, SUBUNIT, ZINC-BINDING SITES, AND SUBSTRATE-BINDING SITES.
RX PubMed=21543846; DOI=10.1107/s0907444911007815;
RA Yennawar H., Moller M., Gillilan R., Yennawar N.;
RT "X-ray crystal structure and small-angle X-ray scattering of sheep liver
RT sorbitol dehydrogenase.";
RL Acta Crystallogr. D 67:440-446(2011).
CC -!- FUNCTION: Polyol dehydrogenase that catalyzes the reversible NAD(+)-
CC dependent oxidation of various sugar alcohols. Is mostly active with
CC xylitol, L-iditol and D-sorbitol (D-glucitol) as substrates, leading to
CC the C2-oxidized products D-xylulose, L-sorbose and D-fructose,
CC respectively (PubMed:1459146). Is a key enzyme in the polyol pathway
CC that interconverts glucose and fructose via sorbitol, which constitutes
CC an important alternate route for glucose metabolism (By similarity).
CC May play a role in sperm motility by using sorbitol as an alternative
CC energy source for sperm motility (By similarity).
CC {ECO:0000250|UniProtKB:Q00796, ECO:0000269|PubMed:1459146}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + xylitol = D-xylulose + H(+) + NADH;
CC Xref=Rhea:RHEA:20433, ChEBI:CHEBI:15378, ChEBI:CHEBI:17140,
CC ChEBI:CHEBI:17151, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.9;
CC Evidence={ECO:0000269|PubMed:1459146};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-iditol + NAD(+) = H(+) + keto-L-sorbose + NADH;
CC Xref=Rhea:RHEA:10160, ChEBI:CHEBI:13172, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18202, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.14;
CC Evidence={ECO:0000269|PubMed:1459146};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + keto-D-fructose + NADH = D-sorbitol + NAD(+);
CC Xref=Rhea:RHEA:33031, ChEBI:CHEBI:15378, ChEBI:CHEBI:17924,
CC ChEBI:CHEBI:48095, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:1459146};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21543846};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:21543846};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.6 mM for D-sorbitol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=0.90 mM for xylitol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=3.3 mM for L-iditol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=51 mM for ribitol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=145 mM for D-mannitol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=680 mM for galactitol (at pH 7.4) {ECO:0000269|PubMed:1459146};
CC KM=1.8 mM for D-sorbitol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC KM=0.70 mM for xylitol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC KM=2.5 mM for L-iditol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC KM=5.6 mM for ribitol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC KM=95 mM for D-mannitol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC KM=285 mM for galactitol (at pH 9.9) {ECO:0000269|PubMed:1459146};
CC Note=kcat is 19.6 sec(-1) for D-sorbitol oxidation (at pH 7.4). kcat
CC is 18.2 sec(-1) for xylitol oxidation (at pH 7.4). kcat is 20.4 sec(-
CC 1) for L-iditol oxidation (at pH 7.4). kcat is 20 sec(-1) for ribitol
CC oxidation (at pH 7.4). kcat is 18.2 sec(-1) for D-mannitol oxidation
CC (at pH 7.4). kcat is 20 sec(-1) for galactitol oxidation (at pH 7.4).
CC kcat is 33 sec(-1) for D-sorbitol oxidation (at pH 9.9). kcat is 29.4
CC sec(-1) for xylitol oxidation (at pH 9.9). kcat is 35.5 sec(-1) for
CC L-iditol oxidation (at pH 9.9). kcat is 29.4 sec(-1) for ribitol
CC oxidation (at pH 9.9). kcat is 33 sec(-1) for D-mannitol oxidation
CC (at pH 9.9). kcat is 28.6 sec(-1) for galactitol oxidation (at pH
CC 9.9). {ECO:0000269|PubMed:1459146};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:21543846}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q64442}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64442}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:Q64442}. Note=Associated with mitochondria of
CC the midpiece and near the plasma membrane in the principal piece of the
CC flagellum. Also found in the epididymosome, secreted by the epididymal
CC epithelium and that transfers proteins from the epididymal fluid to the
CC sperm surface. {ECO:0000250|UniProtKB:Q64442}.
CC -!- TISSUE SPECIFICITY: Expressed in liver. {ECO:0000269|PubMed:1459146,
CC ECO:0000269|PubMed:6705798}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR PIR; S10065; S10065.
DR PDB; 3QE3; X-ray; 1.90 A; A=1-354.
DR PDBsum; 3QE3; -.
DR AlphaFoldDB; P07846; -.
DR SMR; P07846; -.
DR STRING; 9940.ENSOARP00000022632; -.
DR ChEMBL; CHEMBL1075154; -.
DR eggNOG; KOG0024; Eukaryota.
DR SABIO-RK; P07846; -.
DR EvolutionaryTrace; P07846; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; TAS:AgBase.
DR GO; GO:0046526; F:D-xylulose reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0003939; F:L-iditol 2-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0051287; F:NAD binding; TAS:AgBase.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0046370; P:fructose biosynthetic process; TAS:AgBase.
DR GO; GO:0006062; P:sorbitol catabolic process; TAS:AgBase.
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; IPR020843; PKS_ER.
DR InterPro; IPR045306; SDH-like.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Cilium; Direct protein sequencing;
KW Flagellum; Membrane; Metal-binding; Mitochondrion; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..354
FT /note="Sorbitol dehydrogenase"
FT /id="PRO_0000160819"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 49
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 153
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 181
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 206
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 270..272
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 294..296
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 296
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21543846"
FT BINDING 297
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:21543846"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 17..22
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 32..42
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 44..51
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 68..76
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 146..165
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 180..191
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 195..202
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 204..213
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 281..286
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 301..309
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 319..324
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:3QE3"
FT HELIX 328..337
FT /evidence="ECO:0007829|PDB:3QE3"
FT STRAND 339..346
FT /evidence="ECO:0007829|PDB:3QE3"
SQ SEQUENCE 354 AA; 37831 MW; D5FE56BC06F87389 CRC64;
AKPAAENLSL VVHGPGDLRL ENYPIPEPGP NEVLLKMHSV GICGSDVHYW QGRIGDFVVK
KPMVLGHEAS GTVVKVGSLV RHLQPGDRVA IQPGAPRQTD EFCKIGRYNL SPTIFFCATP
PDDGNLCRFY KHNANFCYKL PDNVTFEEGA LIEPLSVGIH ACRRAGVTLG NKVLVCGAGP
IGLVNLLAAK AMGAAQVVVT DLSASRLSKA KEVGADFILE ISNESPEEIA KKVEGLLGSK
PEVTIECTGV ETSIQAGIYA THSGGTLVLV GLGSEMTSVP LVHAATREVD IKGVFRYCNT
WPMAISMLAS KSVNVKPLVT HRFPLEKALE AFETSKKGLG LKVMIKCDPS DQNP
