IMDH_BORBU
ID IMDH_BORBU Reviewed; 404 AA.
AC P49058;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000303|PubMed:9268334};
DE Short=IMP dehydrogenase;
DE Short=IMPD;
DE Short=IMPDH {ECO:0000303|PubMed:9268334};
DE EC=1.1.1.205 {ECO:0000269|PubMed:9268334};
GN Name=guaB {ECO:0000303|PubMed:7961392}; OrderedLocusNames=BB_B17;
OS Borreliella burgdorferi (strain ATCC 35210 / DSM 4680 / CIP 102532 / B31)
OS (Borrelia burgdorferi).
OG Plasmid cp26 (circular 26 kb).
OC Bacteria; Spirochaetes; Spirochaetales; Borreliaceae; Borreliella.
OX NCBI_TaxID=224326;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 35210 / DSM 4680 / CIP 102532 / B31;
RX PubMed=7961392; DOI=10.1128/jb.176.21.6427-6432.1994;
RA Margolis N., Hogan D., Tilly K., Rosa P.;
RT "Plasmid location of Borrelia purine biosynthesis gene homologs.";
RL J. Bacteriol. 176:6427-6432(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35210 / DSM 4680 / CIP 102532 / B31;
RX PubMed=9403685; DOI=10.1038/37551;
RA Fraser C.M., Casjens S., Huang W.M., Sutton G.G., Clayton R.A.,
RA Lathigra R., White O., Ketchum K.A., Dodson R.J., Hickey E.K., Gwinn M.L.,
RA Dougherty B.A., Tomb J.-F., Fleischmann R.D., Richardson D.L.,
RA Peterson J.D., Kerlavage A.R., Quackenbush J., Salzberg S.L., Hanson M.,
RA van Vugt R., Palmer N., Adams M.D., Gocayne J.D., Weidman J.F.,
RA Utterback T.R., Watthey L., McDonald L.A., Artiach P., Bowman C.,
RA Garland S.A., Fujii C., Cotton M.D., Horst K., Roberts K.M., Hatch B.,
RA Smith H.O., Venter J.C.;
RT "Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.";
RL Nature 390:580-586(1997).
RN [3]
RP PROTEIN SEQUENCE OF 2-7, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND SUBUNIT.
RC STRAIN=ATCC 35210 / DSM 4680 / CIP 102532 / B31;
RX PubMed=9268334; DOI=10.1074/jbc.272.35.21977;
RA Zhou X., Cahoon M., Rosa P., Hedstrom L.;
RT "Expression, purification, and characterization of inosine 5'-monophosphate
RT dehydrogenase from Borrelia burgdorferi.";
RL J. Biol. Chem. 272:21977-21981(1997).
RN [4]
RP FUNCTION.
RC STRAIN=ATCC 35210 / DSM 4680 / CIP 102532 / B31;
RX PubMed=19666713; DOI=10.1128/jb.00450-09;
RA Jewett M.W., Lawrence K.A., Bestor A., Byram R., Gherardini F., Rosa P.A.;
RT "GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-
RT mouse infection cycle.";
RL J. Bacteriol. 191:6231-6241(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=10758003; DOI=10.1021/bi992645l;
RA McMillan F.M., Cahoon M., White A., Hedstrom L., Petsko G.A., Ringe D.;
RT "Crystal structure at 2.4-A resolution of Borrelia burgdorferi inosine 5'-
RT monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid
RT motion by loop 6.";
RL Biochemistry 39:4533-4542(2000).
CC -!- FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to
CC xanthosine 5'-phosphate (XMP), the first committed and rate-limiting
CC step in the de novo synthesis of guanine nucleotides, and therefore
CC plays an important role in the regulation of cell growth. Essential for
CC mouse infection by tick bite and critical for the survival in
CC environments that appear to lack sufficient amounts of guanine,
CC guanosine, and/or deoxyguanosine to support spirochete growth, such as
CC mammalian host tissues. {ECO:0000269|PubMed:19666713,
CC ECO:0000269|PubMed:9268334}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + IMP + NAD(+) = H(+) + NADH + XMP; Xref=Rhea:RHEA:11708,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57464,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58053;
CC EC=1.1.1.205; Evidence={ECO:0000269|PubMed:9268334};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000269|PubMed:9268334};
CC -!- ACTIVITY REGULATION: Mycophenolic acid (MPA) is a non-competitive
CC inhibitor that prevents formation of the closed enzyme conformation by
CC binding to the same site as the amobile flap. In contrast, mizoribine
CC monophosphate (MZP) is a competitive inhibitor that induces the closed
CC conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor
CC inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of
CC bacterial IMPDH. {ECO:0000250|UniProtKB:P0ADG7}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:9268334};
CC KM=1100 uM for NAD(+) {ECO:0000269|PubMed:9268334};
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000305|PubMed:9268334}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:9268334}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000305}.
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DR EMBL; U13372; AAA53247.1; -; Genomic_DNA.
DR EMBL; AE000792; AAC66314.1; -; Genomic_DNA.
DR PIR; E70218; E70218.
DR RefSeq; NP_047003.1; NC_001903.1.
DR RefSeq; WP_010890582.1; NC_001903.1.
DR PDB; 1EEP; X-ray; 2.40 A; A/B=1-404.
DR PDBsum; 1EEP; -.
DR AlphaFoldDB; P49058; -.
DR SMR; P49058; -.
DR BindingDB; P49058; -.
DR PRIDE; P49058; -.
DR EnsemblBacteria; AAC66314; AAC66314; BB_B17.
DR KEGG; bbu:BB_B17; -.
DR PATRIC; fig|224326.49.peg.1605; -.
DR HOGENOM; CLU_022552_5_3_12; -.
DR OMA; MGYCGAK; -.
DR BRENDA; 1.1.1.205; 902.
DR SABIO-RK; P49058; -.
DR UniPathway; UPA00601; UER00295.
DR EvolutionaryTrace; P49058; -.
DR Proteomes; UP000001807; Plasmid cp26.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 2.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005990; IMP_DH.
DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR PANTHER; PTHR11911; PTHR11911; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; GMP biosynthesis; Metal-binding;
KW NAD; Oxidoreductase; Plasmid; Potassium; Purine biosynthesis;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9268334"
FT CHAIN 2..404
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093692"
FT ACT_SITE 229
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT ACT_SITE 325
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKI7"
FT BINDING 172
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 222..224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 224
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 226
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 227
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 229
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 262..264
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 285..286
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 309..313
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 340
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 394
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 395
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 396
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:1EEP"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 56..65
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 154..163
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 179..191
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:1EEP"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 230..235
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 241..252
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 268..277
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 286..289
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 352..370
FT /evidence="ECO:0007829|PDB:1EEP"
FT HELIX 375..380
FT /evidence="ECO:0007829|PDB:1EEP"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:1EEP"
SQ SEQUENCE 404 AA; 43768 MW; A91D6D6C5CE522F1 CRC64;
MPNKITKEAL TFDDVSLIPR KSSVLPSEVS LKTQLTKNIS LNIPFLSSAM DTVTESQMAI
AIAKEGGIGI IHKNMSIEAQ RKEIEKVKTY KFQKTINTNG DTNEQKPEIF TAKQHLEKSD
AYKNAEHKED FPNACKDLNN KLRVGAAVSI DIDTIERVEE LVKAHVDILV IDSAHGHSTR
IIELIKKIKT KYPNLDLIAG NIVTKEAALD LISVGADCLK VGIGPGSICT TRIVAGVGVP
QITAICDVYE ACNNTNICII ADGGIRFSGD VVKAIAAGAD SVMIGNLFAG TKESPSEEII
YNGKKFKSYV GMGSISAMKR GSKSRYFQLE NNEPKKLVPE GIEGMVPYSG KLKDILTQLK
GGLMSGMGYL GAATISDLKI NSKFVKISHS SLKESHPHDV FSIT
