UDG_STRPY
ID UDG_STRPY Reviewed; 402 AA.
AC P0C0F4; Q07172;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=UDP-glucose 6-dehydrogenase;
DE Short=UDP-Glc dehydrogenase;
DE Short=UDP-GlcDH;
DE Short=UDPGDH;
DE EC=1.1.1.22 {ECO:0000269|PubMed:14686915};
GN Name=hasB;
OS Streptococcus pyogenes.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=1314;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=WF50;
RX PubMed=8463246; DOI=10.1016/s0021-9258(18)53153-7;
RA Dougherty B.A., van de Rijn I.;
RT "Molecular characterization of hasB from an operon required for hyaluronic
RT acid synthesis in group A streptococci. Demonstration of UDP-glucose
RT dehydrogenase activity.";
RL J. Biol. Chem. 268:7118-7124(1993).
RN [2]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, AND
RP MUTAGENESIS OF THR-118; GLU-141; GLU-145 AND CYS-260.
RX PubMed=14686915; DOI=10.1046/j.1432-1033.2003.03876.x;
RA Ge X., Penney L.C., van de Rijn I., Tanner M.E.;
RT "Active site residues and mechanism of UDP-glucose dehydrogenase.";
RL Eur. J. Biochem. 271:14-22(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND NAD,
RP AND MUTAGENESIS OF CYS-260.
RX PubMed=10841783; DOI=10.1021/bi000181h;
RA Campbell R.E., Mosimann S.C., van De Rijn I., Tanner M.E., Strynadka N.C.;
RT "The first structure of UDP-glucose dehydrogenase reveals the catalytic
RT residues necessary for the two-fold oxidation.";
RL Biochemistry 39:7012-7023(2000).
CC -!- FUNCTION: Catalyzes the formation of UDP-glucuronic acid which is
CC required for capsular hyaluronic acid synthesis.
CC {ECO:0000305|PubMed:8463246}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + 2 NAD(+) + UDP-alpha-D-glucose = 3 H(+) + 2 NADH + UDP-
CC alpha-D-glucuronate; Xref=Rhea:RHEA:23596, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58885; EC=1.1.1.22;
CC Evidence={ECO:0000269|PubMed:14686915};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for UDP-glucose {ECO:0000269|PubMed:14686915};
CC KM=65 uM for NAD {ECO:0000269|PubMed:14686915};
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-alpha-D-glucuronate
CC biosynthesis; UDP-alpha-D-glucuronate from UDP-alpha-D-glucose: step
CC 1/1.
CC -!- SIMILARITY: Belongs to the UDP-glucose/GDP-mannose dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; L08444; AAA26899.1; -; Genomic_DNA.
DR RefSeq; WP_011018341.1; NZ_WXZH01000038.1.
DR PDB; 1DLI; X-ray; 2.31 A; A=1-402.
DR PDB; 1DLJ; X-ray; 1.80 A; A=1-402.
DR PDBsum; 1DLI; -.
DR PDBsum; 1DLJ; -.
DR AlphaFoldDB; P0C0F4; -.
DR SMR; P0C0F4; -.
DR ChEMBL; CHEMBL4523177; -.
DR DrugBank; DB03041; UDP-alpha-D-glucuronic acid.
DR DrugBank; DB01713; UDP-alpha-D-xylose.
DR PATRIC; fig|1314.199.peg.1793; -.
DR eggNOG; COG1004; Bacteria.
DR SABIO-RK; P0C0F4; -.
DR UniPathway; UPA00038; UER00491.
DR EvolutionaryTrace; P0C0F4; -.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0003979; F:UDP-glucose 6-dehydrogenase activity; IDA:CACAO.
DR GO; GO:0000271; P:polysaccharide biosynthetic process; IEA:InterPro.
DR GO; GO:0006065; P:UDP-glucuronate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR017476; UDP-Glc/GDP-Man.
DR InterPro; IPR014027; UDP-Glc/GDP-Man_DH_C.
DR InterPro; IPR036220; UDP-Glc/GDP-Man_DH_C_sf.
DR InterPro; IPR014026; UDP-Glc/GDP-Man_DH_dimer.
DR InterPro; IPR001732; UDP-Glc/GDP-Man_DH_N.
DR InterPro; IPR028357; UDPglc_DH_bac.
DR Pfam; PF00984; UDPG_MGDP_dh; 1.
DR Pfam; PF03720; UDPG_MGDP_dh_C; 1.
DR Pfam; PF03721; UDPG_MGDP_dh_N; 1.
DR PIRSF; PIRSF500134; UDPglc_DH_bac; 1.
DR PIRSF; PIRSF000124; UDPglc_GDPman_dh; 1.
DR SMART; SM00984; UDPG_MGDP_dh_C; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52413; SSF52413; 1.
DR TIGRFAMs; TIGR03026; NDP-sugDHase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Capsule biogenesis/degradation; NAD; Oxidoreductase.
FT CHAIN 1..402
FT /note="UDP-glucose 6-dehydrogenase"
FT /id="PRO_0000074054"
FT ACT_SITE 260
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:14686915"
FT BINDING 2..19
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 29
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 34
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 83
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 118
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 142..145
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783,
FT ECO:0007744|PDB:1DLI"
FT BINDING 145
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 249..253
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783,
FT ECO:0007744|PDB:1DLI"
FT BINDING 257
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 263
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 319
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 320
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 327
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10841783"
FT BINDING 402
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10841783"
FT MUTAGEN 118
FT /note="T->A: Increases Km for substrate 3-fold. Increases
FT Km for NAD 6-fold. Reduces catalytic activity 160-fold."
FT /evidence="ECO:0000269|PubMed:14686915"
FT MUTAGEN 141
FT /note="E->Q: Increases Km for substrate 3-fold. Increases
FT Km for NAD 2-fold. Reduces catalytic activity about 10-
FT fold."
FT /evidence="ECO:0000269|PubMed:14686915"
FT MUTAGEN 145
FT /note="E->Q: Increases Km for substrate 6-fold. Increases
FT Km for NAD 3-fold. Reduces catalytic activity about 10-
FT fold."
FT /evidence="ECO:0000269|PubMed:14686915"
FT MUTAGEN 260
FT /note="C->A,S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10841783,
FT ECO:0000269|PubMed:14686915"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 10..19
FT /evidence="ECO:0007829|PDB:1DLJ"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 23..28
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 48..56
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 67..73
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:1DLJ"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 168..184
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:1DLI"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 197..227
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:1DLJ"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 260..272
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 279..302
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 330..339
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 367..373
FT /evidence="ECO:0007829|PDB:1DLJ"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:1DLJ"
FT HELIX 384..392
FT /evidence="ECO:0007829|PDB:1DLJ"
SQ SEQUENCE 402 AA; 45483 MW; DD1869D659F4CA58 CRC64;
MKIAVAGSGY VGLSLGVLLS LQNEVTIVDI LPSKVDKINN GLSPIQDEYI EYYLKSKQLS
IKATLDSKAA YKEAELVIIA TPTNYNSRIN YFDTQHVETV IKEVLSVNSH ATLIIKSTIP
IGFITEMRQK FQTDRIIFSP EFLRESKALY DNLYPSRIIV SCEENDSPKV KADAEKFALL
LKSAAKKNNV PVLIMGASEA EAVKLFANTY LALRVAYFNE LDTYAESRKL NSHMIIQGIS
YDDRIGMHYN NPSFGYGGYC LPKDTKQLLA NYNNIPQTLI EAIVSSNNVR KSYIAKQIIN
VLKEQESPVK VVGVYRLIMK SNSDNFRESA IKDVIDILKS KDIKIIIYEP MLNKLESEDQ
SVLVNDLENF KKQANIIVTN RYDNELQDVK NKVYSRDIFG RD
