IMDH_CANAX
ID IMDH_CANAX Reviewed; 521 AA.
AC O00086;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 122.
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};
GN Name=IMH3; Synonyms=IMD3;
OS Candida albicans (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=5476;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=SS;
RX PubMed=9079920; DOI=10.1128/jb.179.7.2331-2338.1997;
RA Koehler G.A., White T.C., Agabian N.;
RT "Overexpression of a cloned IMP dehydrogenase gene of Candida albicans
RT confers resistance to the specific inhibitor mycophenolic acid.";
RL J. Bacteriol. 179:2331-2338(1997).
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:9079920}.
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. {ECO:0000255|HAMAP-
CC Rule:MF_03156, ECO:0000269|PubMed:9079920}.
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: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- DEVELOPMENTAL STAGE: Expressed at equal levels in the yeast or hyphal
CC form.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; U85049; AAB51509.1; -; Genomic_DNA.
DR AlphaFoldDB; O00086; -.
DR SMR; O00086; -.
DR COMPLUYEAST-2DPAGE; O00086; -.
DR VEuPathDB; FungiDB:C2_06390C_A; -.
DR VEuPathDB; FungiDB:CAWG_04382; -.
DR PhylomeDB; O00086; -.
DR UniPathway; UPA00601; UER00295.
DR GO; GO:0005737; C:cytoplasm; 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 2: Evidence at transcript level;
KW CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD;
KW Oxidoreductase; Potassium; Purine biosynthesis; Repeat.
FT CHAIN 1..521
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093685"
FT DOMAIN 119..178
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 182..238
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 333
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 435
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 276..278
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 326..328
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 328
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 330
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 331
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 333
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 366..368
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 389..390
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 413..417
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 447
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 506
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 507
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 508
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 521 AA; 56239 MW; 5F1E52611B1E1418 CRC64;
MVFETSKATS YLKDYPKKDG LSVKELIDST NFGGLTYNDF LILPGLINFP SSAVSLETKL
TKKITLKSPF VSSPMDTVTE ENMAIHMALL GGIGIIHHNC TSEEQAEMVR KVKKYENGFI
NDPVVISPEV TVGEVKKMGE VLGFTSFPVT ENGKVGGKLV GIITSRDIQF HEDNKSPVSE
VMTKDLVVGK KGISLTDGNE LLRSSKKGKL PIVDAEGNLV SLISRTDLQK NQDYPNASKS
FHSKQLLCGA AIGTIDADRE RLDKLVEAGL DVVVLDSSNG SSVFQLNMIK WIKEKYPELQ
VIAGNVVTRE QAALLIEAGA DALRIGMGSG SICITQEVMA CGRPQGTAVY GVTEFANKFG
VPCIADGGIG NIGHITKALA LGASCVMMGG LLAGTAETPG DYFYRDGKRL KTYRGMGSID
AMQQTNTNAN ASTSRYFSEA DKVLVAQGVS GSVVDKGSIT KFVPYLYNGL QHSLQDIGIK
SIDELRENVD NGEIRFEFRT ASAQFEGGVH GLHSYEKRLH N
