ALGD_PSEAE
ID ALGD_PSEAE Reviewed; 436 AA.
AC P11759; Q9HY71;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=GDP-mannose 6-dehydrogenase {ECO:0000303|PubMed:3108855};
DE Short=GMD {ECO:0000303|PubMed:3108855};
DE EC=1.1.1.132 {ECO:0000269|PubMed:2470755};
DE AltName: Full=Guanosine diphospho-D-mannose dehydrogenase {ECO:0000303|PubMed:1370473};
GN Name=algD {ECO:0000303|PubMed:3108855}; OrderedLocusNames=PA3540;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND INDUCTION.
RC STRAIN=8830;
RX PubMed=3108855; DOI=10.1093/nar/15.11.4567;
RA Deretic V., Gill J.F., Chakrabarty A.M.;
RT "Pseudomonas aeruginosa infection in cystic fibrosis: nucleotide sequence
RT and transcriptional regulation of the algD gene.";
RL Nucleic Acids Res. 15:4567-4581(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP PROTEIN SEQUENCE OF 1-11, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=8830;
RX PubMed=2470755; DOI=10.1016/s0021-9258(18)60542-3;
RA Roychoudhury S., May T.B., Gill J.F., Singh S.K., Feingold D.S.,
RA Chakrabarty A.M.;
RT "Purification and characterization of guanosine diphospho-D-mannose
RT dehydrogenase. A key enzyme in the biosynthesis of alginate by Pseudomonas
RT aeruginosa.";
RL J. Biol. Chem. 264:9380-9385(1989).
RN [4]
RP PROTEIN SEQUENCE OF 1-11; 280-289 AND 297-306, CATALYTIC ACTIVITY, AND
RP DOMAIN.
RC STRAIN=8830;
RX PubMed=1370473; DOI=10.1016/s0021-9258(18)48384-6;
RA Roychoudhury S., Chakrabarty K., Ho Y.-K., Chakrabarty A.M.;
RT "Characterization of guanosine diphospho-D-mannose dehydrogenase from
RT Pseudomonas aeruginosa. Structural analysis by limited proteolysis.";
RL J. Biol. Chem. 267:990-996(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 425-435.
RC STRAIN=8830;
RX PubMed=8294014; DOI=10.1016/0378-1119(93)90477-k;
RA Maharaj R., May T.B., Wang S.-K., Chakrabarty A.M.;
RT "Sequence of the alg8 and alg44 genes involved in the synthesis of alginate
RT by Pseudomonas aeruginosa.";
RL Gene 136:267-269(1993).
RN [6]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=12135385; DOI=10.1021/bi025862m;
RA Naught L.E., Gilbert S., Imhoff R., Snook C., Beamer L., Tipton P.;
RT "Allosterism and cooperativity in Pseudomonas aeruginosa GDP-mannose
RT dehydrogenase.";
RL Biochemistry 41:9637-9645(2002).
RN [7] {ECO:0007744|PDB:1MFZ, ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH NAD AND PRODUCT,
RP FUNCTION, ACTIVE SITE, SUBUNIT, AND PATHWAY.
RX PubMed=12705829; DOI=10.1021/bi027328k;
RA Snook C.F., Tipton P.A., Beamer L.J.;
RT "Crystal structure of GDP-mannose dehydrogenase: a key enzyme of alginate
RT biosynthesis in P. aeruginosa.";
RL Biochemistry 42:4658-4668(2003).
CC -!- FUNCTION: Catalyzes the oxidation of guanosine diphospho-D-mannose
CC (GDP-D-mannose) to GDP-D-mannuronic acid, a precursor for alginate
CC polymerization. The alginate layer causes a mucoid phenotype and
CC provides a protective barrier against host immune defenses and
CC antibiotics (Probable). Other sugars are not used as substrates
CC (PubMed:2470755). {ECO:0000269|PubMed:2470755,
CC ECO:0000305|PubMed:12705829, ECO:0000305|PubMed:2470755,
CC ECO:0000305|PubMed:3108855}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-alpha-D-mannose + H2O + 2 NAD(+) = GDP-alpha-D-mannuronate
CC + 3 H(+) + 2 NADH; Xref=Rhea:RHEA:21728, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57527, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:84886; EC=1.1.1.132;
CC Evidence={ECO:0000269|PubMed:12135385, ECO:0000269|PubMed:1370473,
CC ECO:0000269|PubMed:2470755};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21729;
CC Evidence={ECO:0000269|PubMed:12135385, ECO:0000269|PubMed:1370473,
CC ECO:0000269|PubMed:2470755};
CC -!- ACTIVITY REGULATION: Inhibited by GMP, ATP, GDP-D-glucose and maltose
CC (PubMed:2470755). Inhibited by GMP and deamidoNAD (PubMed:12135385).
CC {ECO:0000269|PubMed:12135385, ECO:0000269|PubMed:2470755}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.9 uM for GDP-D-mannose {ECO:0000269|PubMed:2470755};
CC KM=4.1 uM for GDP-D-mannose {ECO:0000269|PubMed:12135385};
CC KM=185 uM for NAD(+) {ECO:0000269|PubMed:2470755};
CC KM=92 uM for NAD(+) {ECO:0000269|PubMed:12135385};
CC Vmax=581.4 nmol/min/mg enzyme {ECO:0000269|PubMed:2470755};
CC pH dependence:
CC Optimum pH is 7.7. {ECO:0000269|PubMed:2470755};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius. Stable at 57.5 degrees
CC Celsius, pH 5.0 for 10 minutes, used to purify protein.
CC {ECO:0000269|PubMed:2470755};
CC -!- PATHWAY: Glycan biosynthesis; alginate biosynthesis.
CC {ECO:0000305|PubMed:12705829, ECO:0000305|PubMed:3108855}.
CC -!- SUBUNIT: Forms a domain-swapped dimer with each peptide contributing to
CC each active site. The dimers assemble further (PubMed:12705829). X-ray
CC structures indicate this enzyme exists as a homotetramer
CC PubMed:12705829, but kinetic and physical results obtained in
CC PubMed:2470755 and PubMed:12135385 indicate that it is probably a
CC homohexamer (Probable). {ECO:0000269|PubMed:12705829,
CC ECO:0000305|PubMed:12135385, ECO:0000305|PubMed:12705829,
CC ECO:0000305|PubMed:2470755}.
CC -!- INDUCTION: Highly expressed in mucoid but not non-mucoid cells,
CC probably activated by algR. {ECO:0000269|PubMed:3108855}.
CC -!- DOMAIN: The N-terminus (about 270 residues) binds NAD(+) and GDP-alpha-
CC D-mannose and is joined to C-terminal domain by an exposed linker.
CC {ECO:0000269|PubMed:1370473}.
CC -!- SIMILARITY: Belongs to the UDP-glucose/GDP-mannose dehydrogenase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Slime with a design - Issue
CC 37 of August 2003;
CC URL="https://web.expasy.org/spotlight/back_issues/037";
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DR EMBL; Y00337; CAA68425.1; -; Genomic_DNA.
DR EMBL; AE004091; AAG06928.1; -; Genomic_DNA.
DR EMBL; L22611; AAC36874.1; -; Genomic_DNA.
DR PIR; H83203; H83203.
DR PIR; S07391; DEPSGD.
DR RefSeq; NP_252230.1; NC_002516.2.
DR RefSeq; WP_003110461.1; NZ_QZGE01000001.1.
DR PDB; 1MFZ; X-ray; 2.80 A; A/B/C/D=1-436.
DR PDB; 1MUU; X-ray; 2.02 A; A/B/C/D=1-436.
DR PDB; 1MV8; X-ray; 1.55 A; A/B/C/D=1-436.
DR PDBsum; 1MFZ; -.
DR PDBsum; 1MUU; -.
DR PDBsum; 1MV8; -.
DR AlphaFoldDB; P11759; -.
DR SMR; P11759; -.
DR STRING; 287.DR97_4402; -.
DR DrugBank; DB04023; GDP-alpha-D-mannuronic acid.
DR PaxDb; P11759; -.
DR EnsemblBacteria; AAG06928; AAG06928; PA3540.
DR GeneID; 879004; -.
DR KEGG; pae:PA3540; -.
DR PATRIC; fig|208964.12.peg.3704; -.
DR PseudoCAP; PA3540; -.
DR HOGENOM; CLU_023810_1_1_6; -.
DR InParanoid; P11759; -.
DR OMA; KYADNAF; -.
DR PhylomeDB; P11759; -.
DR BioCyc; MetaCyc:MON-14396; -.
DR BioCyc; PAER208964:G1FZ6-3608-MON; -.
DR BRENDA; 1.1.1.132; 5087.
DR UniPathway; UPA00286; -.
DR EvolutionaryTrace; P11759; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0047919; F:GDP-mannose 6-dehydrogenase activity; IDA:PseudoCAP.
DR GO; GO:0051287; F:NAD binding; IDA:PseudoCAP.
DR GO; GO:0042121; P:alginic acid biosynthetic process; IDA:PseudoCAP.
DR GO; GO:0036460; P:cellular response to cell envelope stress; IDA:PseudoCAP.
DR GO; GO:0006970; P:response to osmotic stress; IDA:PseudoCAP.
DR GO; GO:0044010; P:single-species biofilm formation; IDA:PseudoCAP.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR028358; GDPman_DH.
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 Pfam; PF00984; UDPG_MGDP_dh; 1.
DR Pfam; PF03720; UDPG_MGDP_dh_C; 1.
DR Pfam; PF03721; UDPG_MGDP_dh_N; 1.
DR PIRSF; PIRSF500135; GDPman_DH; 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; Alginate biosynthesis; Direct protein sequencing; NAD;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..436
FT /note="GDP-mannose 6-dehydrogenase"
FT /id="PRO_0000074067"
FT REGION 1..270
FT /note="Substrate-binding region"
FT /evidence="ECO:0000269|PubMed:1370473"
FT REGION 278..295
FT /note="Inter-domain linker"
FT /evidence="ECO:0000269|PubMed:1370473"
FT ACT_SITE 268
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 10..11
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 30
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 35
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 86
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 105
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 124
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 157..161
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 210..217
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 256..265
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 271
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT BINDING 324
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12705829"
FT BINDING 331
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:12705829,
FT ECO:0007744|PDB:1MUU, ECO:0007744|PDB:1MV8"
FT VARIANT 349
FT /note="L -> F (in strain: 3380)"
FT /evidence="ECO:0000305|PubMed:12135385"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 12..21
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 70..75
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 97..110
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:1MV8"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 164..169
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 203..233
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 238..245
FT /evidence="ECO:0007829|PDB:1MV8"
FT TURN 249..253
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 269..282
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 293..308
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 334..344
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 348..352
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 354..359
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 366..371
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 384..390
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 392..396
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 401..403
FT /evidence="ECO:0007829|PDB:1MV8"
FT HELIX 404..408
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 415..421
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:1MV8"
FT STRAND 429..434
FT /evidence="ECO:0007829|PDB:1MV8"
SQ SEQUENCE 436 AA; 47600 MW; B6F3DC2B70B04463 CRC64;
MRISIFGLGY VGAVCAGCLS ARGHEVIGVD VSSTKIDLIN QGKSPIVEPG LEALLQQGRQ
TGRLSGTTDF KKAVLDSDVS FICVGTPSKK NGDLDLGYIE TVCREIGFAI REKSERHTVV
VRSTVLPGTV NNVVIPLIED CSGKKAGVDF GVGTNPEFLR ESTAIKDYDF PPMTVIGELD
KQTGDLLEEI YRELDAPIIR KTVEVAEMIK YTCNVWHAAK VTFANEIGNI AKAVGVDGRE
VMDVICQDHK LNLSRYYMRP GFAFGGSCLP KDVRALTYRA SQLDVEHPML GSLMRSNSNQ
VQKAFDLITS HDTRKVGLLG LSFKAGTDDL RESPLVELAE MLIGKGYELR IFDRNVEYAR
VHGANKEYIE SKIPHVSSLL VSDLDEVVAS SDVLVLGNGD ELFVDLVNKT PSGKKLVDLV
GFMPHTTTAQ AEGICW
