IMDH_ECOLI
ID IMDH_ECOLI Reviewed; 488 AA.
AC P0ADG7; P06981; P76574; P78202;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01964};
DE Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01964};
DE Short=IMPD {ECO:0000255|HAMAP-Rule:MF_01964};
DE Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_01964};
DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_01964};
GN Name=guaB {ECO:0000255|HAMAP-Rule:MF_01964}; Synonyms=guaR;
GN OrderedLocusNames=b2508, JW5401;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2860637; DOI=10.1093/nar/13.4.1303;
RA Tiedeman A.A., Smith J.M.;
RT "Nucleotide sequence of the guaB locus encoding IMP dehydrogenase of
RT Escherichia coli K12.";
RL Nucleic Acids Res. 13:1303-1316(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT its sequence features.";
RL DNA Res. 4:91-113(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
RX PubMed=2998937; DOI=10.1016/0378-1119(85)90068-x;
RA Thomas M.S., Drabble W.T.;
RT "Nucleotide sequence and organisation of the gua promoter region of
RT Escherichia coli.";
RL Gene 36:45-53(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-90.
RX PubMed=1736096; DOI=10.1007/bf00279799;
RA Tesfa-Selase F., Drabble W.T.;
RT "Regulation of the gua operon of Escherichia coli by the DnaA protein.";
RL Mol. Gen. Genet. 231:256-264(1992).
RN [7]
RP PROTEIN SEQUENCE OF 1-12.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [8]
RP PARTIAL PROTEIN SEQUENCE OF 1-11.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.;
RL Submitted (FEB-1996) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 1-5.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9629924; DOI=10.1002/elps.1150190539;
RA Molloy M.P., Herbert B.R., Walsh B.J., Tyler M.I., Traini M.,
RA Sanchez J.-C., Hochstrasser D.F., Williams K.L., Gooley A.A.;
RT "Extraction of membrane proteins by differential solubilization for
RT separation using two-dimensional gel electrophoresis.";
RL Electrophoresis 19:837-844(1998).
RN [10]
RP PROTEIN SEQUENCE OF 1-4.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9600841; DOI=10.1006/jmbi.1998.1726;
RA Wilkins M.R., Gasteiger E., Tonella L., Ou K., Tyler M., Sanchez J.-C.,
RA Gooley A.A., Walsh B.J., Bairoch A., Appel R.D., Williams K.L.,
RA Hochstrasser D.F.;
RT "Protein identification with N and C-terminal sequence tags in proteome
RT projects.";
RL J. Mol. Biol. 278:599-608(1998).
RN [11]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF ASP-13; ASP-50; GLU-54; ASP-138; ASP-200; ASP-243; ASP-248;
RP ASP-338; GLU-369; GLU-373 AND GLU-469.
RC STRAIN=K12;
RX PubMed=9341229; DOI=10.1021/bi9714161;
RA Kerr K.M., Hedstrom L.;
RT "The roles of conserved carboxylate residues in IMP dehydrogenase and
RT identification of a transition state analog.";
RL Biochemistry 36:13365-13373(1997).
RN [12]
RP DOMAIN CBS.
RC STRAIN=K12 / BW25113;
RX PubMed=18312263; DOI=10.1111/j.1365-2958.2008.06153.x;
RA Pimkin M., Markham G.D.;
RT "The CBS subdomain of inosine 5'-monophosphate dehydrogenase regulates
RT purine nucleotide turnover.";
RL Mol. Microbiol. 68:342-359(2008).
RN [13]
RP DOMAIN CBS.
RC STRAIN=K12 / BW25113;
RX PubMed=19153081; DOI=10.1074/jbc.m808541200;
RA Pimkin M., Pimkina J., Markham G.D.;
RT "A regulatory role of the Bateman domain of IMP dehydrogenase in adenylate
RT nucleotide biosynthesis.";
RL J. Biol. Chem. 284:7960-7969(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-267 AND LYS-428, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
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.
CC {ECO:0000255|HAMAP-Rule:MF_01964, ECO:0000269|PubMed:9341229}.
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:0000255|HAMAP-Rule:MF_01964};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01964};
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. IMP dehydrogenase subunit of E.coli contains a
CC cysteine at the IMP binding site and is inhibited in a simple
CC competitive manner by GMP. It does not exhibit allosteric properties as
CC does IMP dehydrogenase from B.subtilis or S.typhimurium.
CC {ECO:0000255|HAMAP-Rule:MF_01964, ECO:0000269|PubMed:9341229}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=61 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:9341229};
CC KM=2000 uM for NAD(+) {ECO:0000269|PubMed:9341229};
CC KM=2.8 mM for K(+) {ECO:0000269|PubMed:9341229};
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_01964}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01964,
CC ECO:0000269|PubMed:9341229}.
CC -!- DOMAIN: The CBS domain of IMPDH is a negative trans-regulator of
CC adenylate nucleotide synthesis, and this role is independent of the
CC catalytic function of IMPDH in the de novo GMP biosynthesis. Deletion
CC of the CBS domain derepresses the synthesis of AMP from IMP.
CC {ECO:0000269|PubMed:18312263, ECO:0000269|PubMed:19153081}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_01964}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA26133.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X02209; CAA26133.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC75561.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA16395.2; -; Genomic_DNA.
DR EMBL; M10101; AAB18618.1; -; Genomic_DNA.
DR PIR; C65027; DEECIP.
DR RefSeq; NP_417003.1; NC_000913.3.
DR RefSeq; WP_001299507.1; NZ_STEB01000011.1.
DR AlphaFoldDB; P0ADG7; -.
DR SMR; P0ADG7; -.
DR BioGRID; 4263221; 88.
DR BioGRID; 851324; 1.
DR DIP; DIP-36207N; -.
DR IntAct; P0ADG7; 1.
DR STRING; 511145.b2508; -.
DR BindingDB; P0ADG7; -.
DR ChEMBL; CHEMBL3630; -.
DR iPTMnet; P0ADG7; -.
DR SWISS-2DPAGE; P0ADG7; -.
DR jPOST; P0ADG7; -.
DR PaxDb; P0ADG7; -.
DR PRIDE; P0ADG7; -.
DR EnsemblBacteria; AAC75561; AAC75561; b2508.
DR EnsemblBacteria; BAA16395; BAA16395; BAA16395.
DR GeneID; 66673604; -.
DR GeneID; 946985; -.
DR KEGG; ecj:JW5401; -.
DR KEGG; eco:b2508; -.
DR PATRIC; fig|1411691.4.peg.4229; -.
DR EchoBASE; EB0416; -.
DR eggNOG; COG0516; Bacteria.
DR eggNOG; COG0517; Bacteria.
DR HOGENOM; CLU_022552_2_2_6; -.
DR InParanoid; P0ADG7; -.
DR OMA; MGYCGAK; -.
DR PhylomeDB; P0ADG7; -.
DR BioCyc; EcoCyc:IMP-DEHYDROG-MON; -.
DR BioCyc; MetaCyc:IMP-DEHYDROG-MON; -.
DR SABIO-RK; P0ADG7; -.
DR UniPathway; UPA00601; UER00295.
DR PRO; PR:P0ADG7; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0032991; C:protein-containing complex; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IDA:EcoCyc.
DR GO; GO:1990829; F:C-rich single-stranded DNA binding; IDA:EcoCyc.
DR GO; GO:0097216; F:guanosine tetraphosphate binding; IDA:EcoCyc.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IDA:EcoCyc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:EcoCyc.
DR GO; GO:0006177; P:GMP biosynthetic process; IMP:EcoCyc.
DR GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0009411; P:response to UV; IMP:EcoCyc.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_01964; IMPDH; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005990; IMP_DH.
DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR PANTHER; PTHR11911; PTHR11911; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01302; IMP_dehydrog; 1.
DR PROSITE; PS51371; CBS; 2.
DR PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE 1: Evidence at protein level;
KW Acetylation; CBS domain; Direct protein sequencing; GMP biosynthesis;
KW Metal-binding; NAD; Oxidoreductase; Potassium; Purine biosynthesis;
KW Reference proteome; Repeat.
FT CHAIN 1..488
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093695"
FT DOMAIN 93..149
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT DOMAIN 153..214
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT ACT_SITE 305
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT ACT_SITE 401
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 248..250
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 298..300
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 300
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:0000255|HAMAP-Rule:MF_01964"
FT BINDING 302
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:0000255|HAMAP-Rule:MF_01964"
FT BINDING 303
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 305
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:0000255|HAMAP-Rule:MF_01964"
FT BINDING 338..340
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 361..362
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 385..389
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 415
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 469
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 470
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT BINDING 471
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01964"
FT MOD_RES 267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT MOD_RES 428
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT MUTAGEN 13
FT /note="D->A: Causes a 38-fold increase in the value of Km
FT for K(+). No change is observed in the value of Km for
FT IMP."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 50
FT /note="D->A: Causes a 17-fold increase in the value of Km
FT for K(+)."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 54
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 138
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 200
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 243
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 248
FT /note="D->A: Causes a 130-fold decrease in the value of
FT kcat."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 338
FT /note="D->A: Decreases the value of kcat by 600-fold.
FT Increases the value of Km for IMP by 12-fold."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 369
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 373
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:9341229"
FT MUTAGEN 469
FT /note="E->A: Increases the value of Km for K(+) by 17-
FT fold."
FT /evidence="ECO:0000269|PubMed:9341229"
FT CONFLICT 206
FT /note="R -> A (in Ref. 1; CAA26133/AAB18618)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 52022 MW; B0FD0A786779C98E CRC64;
MLRIAKEALT FDDVLLVPAH STVLPNTADL STQLTKTIRL NIPMLSAAMD TVTEARLAIA
LAQEGGIGFI HKNMSIERQA EEVRRVKKHE SGVVTDPQTV LPTTTLREVK ELTERNGFAG
YPVVTEENEL VGIITGRDVR FVTDLNQPVS VYMTPKERLV TVREGEAREV VLAKMHEKRV
EKALVVDDEF HLIGMITVKD FQKAERKPNA CKDEQGRLRV GAAVGAGAGN EERVDALVAA
GVDVLLIDSS HGHSEGVLQR IRETRAKYPD LQIIGGNVAT AAGARALAEA GCSAVKVGIG
PGSICTTRIV TGVGVPQITA VADAVEALEG TGIPVIADGG IRFSGDIAKA IAAGASAVMV
GSMLAGTEES PGEIELYQGR SYKSYRGMGS LGAMSKGSSD RYFQSDNAAD KLVPEGIEGR
VAYKGRLKEI IHQQMGGLRS CMGLTGCGTI DELRTKAEFV RISGAGIQES HVHDVTITKE
SPNYRLGS
