ID   IMDH_LEIDO              Reviewed;         514 AA.
AC   P21620;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1991, sequence version 1.
DT   13-SEP-2023, entry version 129.
DE   RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPD {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_03156};
DE            EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
OS   Leishmania donovani.
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX   NCBI_TaxID=5661;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1671039; DOI=10.1016/s0021-9258(18)52346-2;
RA   Wilson K.E., Collart F.R., Huberman E., Stringer J.R., Ullman B.;
RT   "Amplification and molecular cloning of the IMP dehydrogenase gene of
RT   Leishmania donovani.";
RL   J. Biol. Chem. 266:1665-1671(1991).
RN   [2]
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR
RP   LOCATION, INTERACTION WITH PEX5, AND SUBUNIT.
RX   PubMed=17173987; DOI=10.1016/j.molbiopara.2006.11.007;
RA   Dobie F., Berg A., Boitz J.M., Jardim A.;
RT   "Kinetic characterization of inosine monophosphate dehydrogenase of
RT   Leishmania donovani.";
RL   Mol. Biochem. Parasitol. 152:11-21(2007).
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_03156, ECO:0000269|PubMed:17173987}.
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_03156};
CC   -!- COFACTOR:
CC       Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03156};
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. Potently inhibited by MPA. Inhibited by XMP and GMP.
CC       {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:17173987}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=33 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:17173987};
CC         KM=390 uM for NAD(+) {ECO:0000269|PubMed:17173987};
CC   -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC       from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC   -!- SUBUNIT: Heterotetramer. Interacts with glycosomal protein sorting
CC       receptor PEX5. {ECO:0000269|PubMed:17173987}.
CC   -!- SUBCELLULAR LOCATION: Glycosome {ECO:0000255|HAMAP-Rule:MF_03156,
CC       ECO:0000269|PubMed:17173987}.
CC   -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC       Rule:MF_03156}.
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DR   EMBL; M55667; AAA29253.1; -; Genomic_DNA.
DR   PIR; A38668; A38668.
DR   RefSeq; XP_003860332.1; XM_003860284.1.
DR   AlphaFoldDB; P21620; -.
DR   SMR; P21620; -.
DR   GeneID; 13386143; -.
DR   KEGG; ldo:LDBPK_191590; -.
DR   VEuPathDB; TriTrypDB:LdBPK_191590.1; -.
DR   VEuPathDB; TriTrypDB:LdCL_190021700; -.
DR   VEuPathDB; TriTrypDB:LDHU3_19.1930; -.
DR   OMA; MGYCGAK; -.
DR   OrthoDB; 166969at2759; -.
DR   BRENDA; 1.1.1.205; 2947.
DR   SABIO-RK; P21620; -.
DR   UniPathway; UPA00601; UER00295.
DR   GO; GO:0020015; C:glycosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
DR   CDD; cd04601; CBS_pair_IMPDH; 1.
DR   CDD; cd00381; IMPDH; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 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   NCBIfam; TIGR01302; IMP_dehydrog; 1.
DR   PANTHER; PTHR11911:SF111; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11911; INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED; 1.
DR   Pfam; PF00571; CBS; 2.
DR   Pfam; PF00478; IMPDH; 1.
DR   PIRSF; PIRSF000130; IMPDH; 1.
DR   SMART; SM00116; CBS; 2.
DR   SMART; SM01240; IMPDH; 1.
DR   SUPFAM; SSF54631; CBS-domain pair; 1.
DR   SUPFAM; SSF51412; Inosine monophosphate dehydrogenase (IMPDH); 1.
DR   PROSITE; PS51371; CBS; 2.
DR   PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE   1: Evidence at protein level;
KW   CBS domain; Glycosome; GMP biosynthesis; Metal-binding; NAD;
KW   Oxidoreductase; Peroxisome; Potassium; Purine biosynthesis; Repeat.
FT   CHAIN           1..514
FT                   /note="Inosine-5'-monophosphate dehydrogenase"
FT                   /id="PRO_0000093675"
FT   DOMAIN          112..171
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   DOMAIN          175..233
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   MOTIF           512..514
FT                   /note="Microbody targeting signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        327
FT                   /note="Thioimidate intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        425
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         270..272
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         320..322
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         322
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_03156"
FT   BINDING         324
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_03156"
FT   BINDING         325
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         327
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_03156"
FT   BINDING         360..362
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         383..384
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         407..411
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         437
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         496
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_03156"
FT   BINDING         497
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_03156"
FT   BINDING         498
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_03156"
SQ   SEQUENCE   514 AA;  55552 MW;  E251FCC1362D60E5 CRC64;
     MATNNANYRI KTIKDGCTAE ELFRGDGLTY NDFIILPGFI DFGAADVNIS GQFTKRIRLH
     IPIVSSPMDT ITENEMAKTM ALMGGVGVLH NNCTVERQVE MVKSVKAYRN GFISKPKSVP
     PNTPISNIIR IKEEKGISGI LVTENGDPHG KLLGIVCTKD IDYVKNKDTP VSAVMTRREK
     MTVERAPIQL EEAMDVLNRS RYGYLPIVNE NDEVVNLCSR RDAVRARDYP HSTLDKSGRL
     ICAAATSTRP EDKRRVAALA DVGVDVLVLD SSQGNTIYQI AFIKWVKSTY PHLEVVAGNV
     VTQDQAKNLI DAGADGIRIG MGSGSICITQ EVLACGRPQG TAVYKVAQYC ASRGVPCTAD
     GGLRQVGDIC KALAIGANCA MLGGMLSGTT ETPGEYFFKG GVRLKVYRGM GSLEAMSQGK
     ESGKRYLSEN EAVQVAQGVS GNVVDKGSAA KLIAYVSKGL QQSAQDIGEI SFDAIREKMY
     AGQVLFSRRS PTAQGEGGVH SLHSYEKKLF AAKM
//