IMDH_LEIDO
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 03-AUG-2022, entry version 126.
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;
CC Evidence={ECO:0000255|HAMAP-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 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; 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 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
