BCS1_HAEIF
ID BCS1_HAEIF Reviewed; 474 AA.
AC Q48230;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Bifunctional ribulose 5-phosphate reductase/CDP-ribitol pyrophosphorylase Bcs1 {ECO:0000305};
DE AltName: Full=CDP-ribitol synthase {ECO:0000303|PubMed:11305920};
DE Includes:
DE RecName: Full=Ribitol-5-phosphate cytidylyltransferase {ECO:0000303|PubMed:11305920};
DE EC=2.7.7.40 {ECO:0000269|PubMed:11305920, ECO:0000269|PubMed:15362865};
DE Includes:
DE RecName: Full=Ribulose-5-phosphate reductase {ECO:0000303|PubMed:11305920};
DE Short=Ribulose-5-P reductase {ECO:0000305};
DE EC=1.1.1.405 {ECO:0000269|PubMed:11305920, ECO:0000269|PubMed:15362865};
DE AltName: Full=Ribitol-5-phosphate dehydrogenase {ECO:0000305};
GN Name=bcs1 {ECO:0000312|EMBL:AAP42161.1};
OS Haemophilus influenzae.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=727 {ECO:0000312|EMBL:CAA55303.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=RM135 {ECO:0000312|EMBL:CAA55303.1};
RX PubMed=7752885; DOI=10.1111/j.1365-2958.1995.tb02225.x;
RA van Eldere J., Brophy L., Loynds B., Celis P., Kroll J.S., Moxon E.R.,
RA Hancock I., Carman S.;
RT "Region II of Haemophilus influenzae type b capsulation locus is involved
RT in serotype-specific polysaccharide synthesis.";
RL Mol. Microbiol. 15:107-118(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=373 / Serotype B {ECO:0000312|EMBL:AAP42171.1}, and
RC GA834 / Serotype B {ECO:0000312|EMBL:AAP42161.1};
RX PubMed=12761153; DOI=10.1128/iai.71.6.3639-3644.2003;
RA Satola S.W., Schirmer P.L., Farley M.M.;
RT "Complete sequence of the cap locus of Haemophilus influenzae serotype b
RT and nonencapsulated b capsule-negative variants.";
RL Infect. Immun. 71:3639-3644(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND MUTAGENESIS OF ARG-18 AND LYS-386.
RX PubMed=11305920; DOI=10.1021/bi002745n;
RA Zolli M., Kobric D.J., Brown E.D.;
RT "Reduction precedes cytidylyl transfer without substrate channeling in
RT distinct active sites of the bifunctional CDP-ribitol synthase from
RT Haemophilus influenzae.";
RL Biochemistry 40:5041-5048(2001).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP ENZYME KINETICS.
RX PubMed=15362865; DOI=10.1021/bi048866v;
RA Pereira M.P., Brown E.D.;
RT "Bifunctional catalysis by CDP-ribitol synthase: convergent recruitment of
RT reductase and cytidylyltransferase activities in Haemophilus influenzae and
RT Staphylococcus aureus.";
RL Biochemistry 43:11802-11812(2004).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of D-ribulose 5-
CC phosphate to D-ribitol 5-phosphate and the further reaction of D-
CC ribitol 5-phosphate with CTP to form CDP-ribitol.
CC {ECO:0000269|PubMed:11305920, ECO:0000269|PubMed:15362865}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + D-ribitol 5-phosphate + H(+) = CDP-L-ribitol +
CC diphosphate; Xref=Rhea:RHEA:12456, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:57608,
CC ChEBI:CHEBI:57695; EC=2.7.7.40;
CC Evidence={ECO:0000269|PubMed:11305920, ECO:0000269|PubMed:15362865};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-ribitol 5-phosphate + NADP(+) = D-ribulose 5-phosphate +
CC H(+) + NADPH; Xref=Rhea:RHEA:19921, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57695, ChEBI:CHEBI:57783, ChEBI:CHEBI:58121,
CC ChEBI:CHEBI:58349; EC=1.1.1.405;
CC Evidence={ECO:0000269|PubMed:11305920, ECO:0000269|PubMed:15362865};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=42 uM for D-ribulose 5-phosphate {ECO:0000269|PubMed:11305920};
CC KM=106 uM for D-ribulose 5-phosphate {ECO:0000269|PubMed:15362865};
CC KM=25 uM for NADPH {ECO:0000269|PubMed:11305920};
CC KM=7.06 uM for NADPH {ECO:0000269|PubMed:15362865};
CC KM=75 uM for D-ribitol 5-phosphate (for the cytidylyltransferase
CC reaction) {ECO:0000269|PubMed:11305920};
CC KM=14.7 uM for D-ribitol 5-phosphate (for the cytidylyltransferase
CC reaction) {ECO:0000269|PubMed:15362865};
CC KM=74 uM for CTP {ECO:0000269|PubMed:11305920};
CC KM=8.51 uM for CTP {ECO:0000269|PubMed:15362865};
CC Note=kcat is 22 sec(-1) for the reductase reaction. kcat is 13 sec(-
CC 1) for the cytidyltransferase reaction.
CC {ECO:0000269|PubMed:11305920};
CC -!- PATHWAY: Capsule biogenesis; capsule polysaccharide biosynthesis.
CC {ECO:0000305}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11305920,
CC ECO:0000269|PubMed:15362865}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the IspD/TarI
CC cytidylyltransferase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the short-chain
CC dehydrogenases/reductases (SDR) family. {ECO:0000305}.
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DR EMBL; AF549210; AAP42161.1; -; Genomic_DNA.
DR EMBL; AF549212; AAP42171.1; -; Genomic_DNA.
DR EMBL; X78559; CAA55303.1; -; Genomic_DNA.
DR PIR; S60902; S60902.
DR AlphaFoldDB; Q48230; -.
DR SMR; Q48230; -.
DR BRENDA; 1.1.1.405; 2529.
DR SABIO-RK; Q48230; -.
DR UniPathway; UPA00934; -.
DR GO; GO:0050518; F:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0047349; F:D-ribitol-5-phosphate cytidylyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd02516; CDP-ME_synthetase; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR HAMAP; MF_00108; IspD; 1.
DR InterPro; IPR012115; CDP-ribitol_syn.
DR InterPro; IPR001228; IspD.
DR InterPro; IPR034683; IspD/TarI.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF01128; IspD; 1.
DR PIRSF; PIRSF036586; CDP-ribitol_syn; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Capsule biogenesis/degradation; NADP; Nucleotidyltransferase;
KW Oxidoreductase; Transferase.
FT CHAIN 1..474
FT /note="Bifunctional ribulose 5-phosphate reductase/CDP-
FT ribitol pyrophosphorylase Bcs1"
FT /id="PRO_0000437506"
FT REGION 1..238
FT /note="Ribitol-5-phosphate cytidylyltransferase"
FT REGION 250..474
FT /note="Ribulose-5-phosphate reductase"
FT MUTAGEN 18
FT /note="R->A: Has 100-fold reduction of catalytic efficiency
FT for the cytidylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11305920"
FT MUTAGEN 386
FT /note="K->A: Has 70-fold reduction of catalytic efficiency
FT for the reductase activity."
FT /evidence="ECO:0000269|PubMed:11305920"
SQ SEQUENCE 474 AA; 52467 MW; DC42A2B245318A95 CRC64;
MNKNKNIGII LAGGVGSRMG LGYPKQFSKI AGKTALEHTL AIFQEHKEID EIIIVSERTS
YRRIEDIVSK LDFSKVNRII FGGKERSDST LSAITALQDE PENTKLIIHD AVRPLLATEI
ISECIAKLDK YNAVDVAIPA VDTIVHVNND TQEIIKIPKR AEYYQGQTPQ AFKLGTLKKA
YDIYTQGGIE GTCDCSIVLK TLPEERVGIV SGSETNIKLT RPVDLFIADK LFQSRSHFSL
RNITSIDRLY DMKDQVLVVI GGSYGIGAHI IDIAKKFGIK TYSLSRSNGV DVGDVKSIEK
AFAEIYAKEH KIDHIVNTAA VLNHKTLVSM SYEEILTSIN VNYTGMINAV ITAYPYLKQT
HGSFLGFTSS SYTRGRPFYA IYSSAKAAVV NLTQAISEEW LPDNIKINCV NPERTKTPMR
TKAFGIEPEG TLLDAKTVAF ASLVVLASRE TGNIIDVVLK DEEYITNILA DLYK
