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 27-MAR-2024, entry version 102. 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; Bacillota; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L08444; AAA26899.1; -; Genomic_DNA. DR RefSeq; WP_011018341.1; NZ_WVFV01000022.1. 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 STRING; 1314.SD89_09600; -. 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 OMA; CLPKDPY; -. 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; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2. 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 NCBIfam; TIGR03026; NDP-sugDHase; 1. DR PANTHER; PTHR43750:SF2; UDP-GLUCOSE 6-DEHYDROGENASE; 1. DR PANTHER; PTHR43750; UDP-GLUCOSE 6-DEHYDROGENASE TUAD; 1. 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; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF52413; UDP-glucose/GDP-mannose dehydrogenase C-terminal domain; 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 FT 10-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 FT 10-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 //