KDUD_ECOLI
ID KDUD_ECOLI Reviewed; 253 AA.
AC P37769; Q2M9Z5;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase {ECO:0000303|PubMed:24509771};
DE EC=1.1.1.127 {ECO:0000269|Ref.4};
DE AltName: Full=2-deoxy-D-gluconate 3-dehydrogenase {ECO:0000303|PubMed:23437267};
DE AltName: Full=2-keto-3-deoxygluconate 5-dehydrogenase;
DE AltName: Full=2-keto-3-deoxygluconate oxidoreductase {ECO:0000303|Ref.4};
DE Short=KDG oxidoreductase;
DE AltName: Full=20-ketosteroid reductase {ECO:0000303|PubMed:24509771};
DE EC=1.1.1.- {ECO:0000269|PubMed:24509771};
GN Name=kduD {ECO:0000303|PubMed:24509771}; Synonyms=ygeC, yqeD;
GN OrderedLocusNames=b2842, JW2810;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 216-253.
RC STRAIN=K12 / JM2433;
RX PubMed=2836407; DOI=10.1016/s0021-9258(18)68433-9;
RA Maiden M.C.J., Jones-Mortimer M.C., Henderson P.J.F.;
RT "The cloning, DNA sequence, and overexpression of the gene araE coding for
RT arabinose-proton symport in Escherichia coli K12.";
RL J. Biol. Chem. 263:8003-8010(1988).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=K12;
RA Hantz O.;
RT "La voie degradative secondaire du 2 ceto 3 desoxygluconate chez
RT Escherichia coli. Oxydation enzymatique du 2 ceto 3 desoxygluconate.";
RL Thesis (1977), Claude Bernard University, France.
RN [5]
RP IDENTIFICATION.
RX PubMed=1766386; DOI=10.1111/j.1365-2958.1991.tb02149.x;
RA Condemine G., Robert-Baudouy J.;
RT "Analysis of an Erwinia chrysanthemi gene cluster involved in pectin
RT degradation.";
RL Mol. Microbiol. 5:2191-2202(1991).
RN [6]
RP TRANSCRIPTIONAL REGULATION.
RC STRAIN=K12;
RX PubMed=15528647; DOI=10.1099/mic.0.27041-0;
RA Rodionov D.A., Gelfand M.S., Hugouvieux-Cotte-Pattat N.;
RT "Comparative genomics of the KdgR regulon in Erwinia chrysanthemi 3937 and
RT other gamma-proteobacteria.";
RL Microbiology 150:3571-3590(2004).
RN [7]
RP INDUCTION.
RC STRAIN=K12;
RX PubMed=22427493; DOI=10.1128/aem.00244-12;
RA Rothe M., Alpert C., Engst W., Musiol S., Loh G., Blaut M.;
RT "Impact of nutritional factors on the proteome of intestinal Escherichia
RT coli: induction of OxyR-dependent proteins AhpF and Dps by a lactose-rich
RT diet.";
RL Appl. Environ. Microbiol. 78:3580-3591(2012).
RN [8]
RP FUNCTION, AND INDUCTION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=23437267; DOI=10.1371/journal.pone.0056906;
RA Rothe M., Alpert C., Loh G., Blaut M.;
RT "Novel insights into E. coli's hexuronate metabolism: KduI facilitates the
RT conversion of galacturonate and glucuronate under osmotic stress
RT conditions.";
RL PLoS ONE 8:E56906-E56906(2013).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, BIOTECHNOLOGY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=K12 / DH5-alpha;
RX PubMed=24509771; DOI=10.1007/s00253-014-5551-8;
RA Tubeleviciute A., Teese M.G., Jose J.;
RT "Escherichia coli kduD encodes an oxidoreductase that converts both sugar
RT and steroid substrates.";
RL Appl. Microbiol. Biotechnol. 98:5471-5485(2014).
CC -!- FUNCTION: Catalyzes the reversible reduction of 2,5-diketo-3-
CC deoxygluconate (DKII or 4,6-dihydroxy-2,5-dioxohexanoate) into 2-keto-
CC 3-deoxygluconate (KDG or 2-dehydro-3-deoxygluconate) with a concomitant
CC oxidation of NADH (Ref.4). To a lesser extent, can also reduce 5-keto-
CC D-gluconate and oxidize D-gluconate and 1,2-propanediol
CC (PubMed:24509771). Together with KduI, seems to play a role in the
CC catabolism of hexuronates under osmotic stress conditions, substituting
CC for the regular hexuronate degrading enzymes UxaABC and UxuAB whose
CC expression is repressed in these conditions (PubMed:23437267). In
CC vitro, also exhibits NADH-dependent 20-ketosteroid reductase activity
CC against eukaryotic steroid hormone 11-deoxycorticosterone (11-DOC),
CC which is converted into the product 4-pregnen-20,21-diol-3-one. In
CC addition to 11-DOC, five other C21 steroid compounds (11-deoxycortisol,
CC cortisol, corticosterone, cortisone, and 21-hydroxypregnenolone) are
CC reduced by KduD, but steroids lacking the hydroxyl group at C21
CC position, such as pregnenolone, testosterone propionate, cortisone
CC acetate, or progesterone, cannot be used as substrate
CC (PubMed:24509771). {ECO:0000269|PubMed:23437267,
CC ECO:0000269|PubMed:24509771, ECO:0000269|Ref.4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-dehydro-3-deoxy-D-gluconate + NAD(+) = 3-deoxy-D-glycero-
CC 2,5-hexodiulosonate + H(+) + NADH; Xref=Rhea:RHEA:24232,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29071, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:57990; EC=1.1.1.127;
CC Evidence={ECO:0000269|Ref.4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-pregnen-20,21-diol-3-one + NAD(+) = 21-hydroxyprogesterone +
CC H(+) + NADH; Xref=Rhea:RHEA:47716, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16973, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:87841; Evidence={ECO:0000269|PubMed:24509771};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 mM for 2-keto-3-deoxygluconate {ECO:0000269|Ref.4};
CC KM=0.230 mM for 11-deoxycorticosterone {ECO:0000269|PubMed:24509771};
CC KM=0.190 mM for 11-deoxycortisol {ECO:0000269|PubMed:24509771};
CC KM=544.8 mM for D-gluconate {ECO:0000269|PubMed:24509771};
CC KM=184.5 mM for 5-keto-D-gluconate {ECO:0000269|PubMed:24509771};
CC KM=3231 mM for 1,2-propanediol {ECO:0000269|PubMed:24509771};
CC KM=0.037 mM for NADH {ECO:0000269|PubMed:24509771};
CC KM=0.285 mM for NAD(+) {ECO:0000269|PubMed:24509771};
CC Note=kcat is 3.1 min(-1) for 11-DOC reduction. kcat is 16.6 min(-1)
CC for 11-deoxycortisol (RSS) reduction. kcat is 58.3 min(-1) for D-
CC gluconate oxidation. kcat is 30.7 min(-1) for 5-keto-D-gluconate
CC reduction. kcat is 18.3 min(-1) for 1,2-propanediol oxidation.
CC {ECO:0000269|PubMed:24509771};
CC pH dependence:
CC Optimum pH is 7.0 for the reduction of 11-DOC, and 9.5 for the
CC oxidation of D-gluconate. {ECO:0000269|PubMed:24509771};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius for the reduction of 11-
CC DOC. {ECO:0000269|PubMed:24509771};
CC -!- SUBUNIT: Homotetramer. {ECO:0000305|PubMed:24509771}.
CC -!- INDUCTION: Is under the control of KdgR repressor (Probable). Its
CC expression is up-regulated in the presence of galacturonate and
CC glucuronate (PubMed:23437267). Is also up-regulated in intestinal
CC E.coli of mice fed a lactose-rich diet and down-regulated in E.coli of
CC mice on a casein-rich diet (PubMed:22427493).
CC {ECO:0000269|PubMed:22427493, ECO:0000269|PubMed:23437267,
CC ECO:0000305|PubMed:15528647}.
CC -!- BIOTECHNOLOGY: Could be used for the production of valuable bioactive
CC 20-hydroxysteroids; these compounds have potential for pharmaceutical
CC applications as inhibitors of steroid hormone metabolizing enzymes, for
CC the treatment of breast cancer, endometriosis, and prostate diseases in
CC humans. {ECO:0000305|PubMed:24509771}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: Most strains of E.coli do not exhibit 20-ketosteroid reductase
CC activity against steroid substrates such as 11-DOC, despite containing
CC a full-length kduD gene. This activity is observed in the K12 / DH5-
CC alpha strain, whose disruption of the kdgR gene leads to the
CC constitutive expression of KduD in this strain.
CC {ECO:0000305|PubMed:24509771}.
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DR EMBL; U29581; AAB40489.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75881.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76911.1; -; Genomic_DNA.
DR EMBL; J03732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; C65067; C65067.
DR RefSeq; NP_417319.1; NC_000913.3.
DR RefSeq; WP_000603502.1; NZ_LN832404.1.
DR AlphaFoldDB; P37769; -.
DR SMR; P37769; -.
DR BioGRID; 4262312; 35.
DR IntAct; P37769; 2.
DR STRING; 511145.b2842; -.
DR jPOST; P37769; -.
DR PaxDb; P37769; -.
DR PRIDE; P37769; -.
DR EnsemblBacteria; AAC75881; AAC75881; b2842.
DR EnsemblBacteria; BAE76911; BAE76911; BAE76911.
DR GeneID; 947323; -.
DR KEGG; ecj:JW2810; -.
DR KEGG; eco:b2842; -.
DR PATRIC; fig|1411691.4.peg.3892; -.
DR EchoBASE; EB2264; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_1_6; -.
DR InParanoid; P37769; -.
DR OMA; RIWDSKV; -.
DR PhylomeDB; P37769; -.
DR BioCyc; EcoCyc:KDUD-MON; -.
DR BioCyc; MetaCyc:KDUD-MON; -.
DR PRO; PR:P37769; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0102635; F:11-deoxycorticosterone reductase activity; IEA:RHEA.
DR GO; GO:0047001; F:2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0008678; F:2-deoxy-D-gluconate 3-dehydrogenase activity; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:EcoCyc.
DR GO; GO:0033764; F:steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:EcoCyc.
DR GO; GO:0019698; P:D-galacturonate catabolic process; IEP:EcoCyc.
DR GO; GO:0042840; P:D-glucuronate catabolic process; IEP:EcoCyc.
DR InterPro; IPR011286; 2-deoxy-D-gluc_3_DH.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01832; kduD; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..253
FT /note="2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase"
FT /id="PRO_0000054715"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 14..38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 145
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 253 AA; 27070 MW; C751D4C2CEC6FAA0 CRC64;
MILSAFSLEG KVAVVTGCDT GLGQGMALGL AQAGCDIVGI NIVEPTETIE QVTALGRRFL
SLTADLRKID GIPALLDRAV AEFGHIDILV NNAGLIRRED ALEFSEKDWD DVMNLNIKSV
FFMSQAAAKH FIAQGNGGKI INIASMLSFQ GGIRVPSYTA SKSGVMGVTR LMANEWAKHN
INVNAIAPGY MATNNTQQLR ADEQRSAEIL DRIPAGRWGL PSDLMGPIVF LASSASDYVN
GYTIAVDGGW LAR
