IMDH_CRYNJ
ID IMDH_CRYNJ Reviewed; 544 AA.
AC Q5KP44; Q55ZT3;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
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 OrderedLocusNames=CNA04240;
OS Cryptococcus neoformans var. neoformans serotype D (strain JEC21 / ATCC
OS MYA-565) (Filobasidiella neoformans).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=214684;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=JEC21 / ATCC MYA-565;
RX PubMed=15653466; DOI=10.1126/science.1103773;
RA Loftus B.J., Fung E., Roncaglia P., Rowley D., Amedeo P., Bruno D.,
RA Vamathevan J., Miranda M., Anderson I.J., Fraser J.A., Allen J.E.,
RA Bosdet I.E., Brent M.R., Chiu R., Doering T.L., Donlin M.J., D'Souza C.A.,
RA Fox D.S., Grinberg V., Fu J., Fukushima M., Haas B.J., Huang J.C.,
RA Janbon G., Jones S.J.M., Koo H.L., Krzywinski M.I., Kwon-Chung K.J.,
RA Lengeler K.B., Maiti R., Marra M.A., Marra R.E., Mathewson C.A.,
RA Mitchell T.G., Pertea M., Riggs F.R., Salzberg S.L., Schein J.E.,
RA Shvartsbeyn A., Shin H., Shumway M., Specht C.A., Suh B.B., Tenney A.,
RA Utterback T.R., Wickes B.L., Wortman J.R., Wye N.H., Kronstad J.W.,
RA Lodge J.K., Heitman J., Davis R.W., Fraser C.M., Hyman R.W.;
RT "The genome of the basidiomycetous yeast and human pathogen Cryptococcus
RT neoformans.";
RL Science 307:1321-1324(2005).
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}.
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. {ECO:0000255|HAMAP-Rule:MF_03156}.
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 -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; AE017341; AAW40949.1; -; Genomic_DNA.
DR RefSeq; XP_566768.1; XM_566768.1.
DR AlphaFoldDB; Q5KP44; -.
DR SMR; Q5KP44; -.
DR STRING; 5207.AAW40949; -.
DR BindingDB; Q5KP44; -.
DR ChEMBL; CHEMBL4295605; -.
DR PaxDb; Q5KP44; -.
DR EnsemblFungi; AAW40949; AAW40949; CNA04240.
DR GeneID; 3253376; -.
DR KEGG; cne:CNA04240; -.
DR VEuPathDB; FungiDB:CNA04240; -.
DR eggNOG; KOG2550; Eukaryota.
DR HOGENOM; CLU_022552_2_1_1; -.
DR InParanoid; Q5KP44; -.
DR OMA; MGYCGAK; -.
DR OrthoDB; 618077at2759; -.
DR UniPathway; UPA00601; UER00295.
DR Proteomes; UP000002149; Chromosome 1.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IBA:GO_Central.
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 GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
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 3: Inferred from homology;
KW CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD;
KW Oxidoreductase; Potassium; Purine biosynthesis; Reference proteome; Repeat.
FT CHAIN 1..544
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000415685"
FT DOMAIN 132..192
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 194..250
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 345
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 458
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 288..290
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 338..340
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 340
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 342
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 343
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 345
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 378..380
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 401..402
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 425..429
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 470
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 529
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 530
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 531
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 544 AA; 57899 MW; E5AB349D78F302AB CRC64;
MADTNPNAPP RSDSLLNPAD ALKYLEEYPR GDGLSLQELM DSRKNGGLTY NDFLVLPGHI
SFPASDVSLQ SRATKNIVLN TPFLSSPMDT VTEDRMAIAL ALHGGLGIIH HNCSAEEQAA
MVRRVKKYEN GFITDPLCLG PDATVGDVLE IKAKFGFCGV PITETGAPNS KLLGIVTGRD
VQFQDAETPI KSVMTTEVVT GSSPITLEKA NSLLRETKKG KLPIVDSNGH LVSLVARSDL
LKNQNYPYAS KVPESKQLYC GAAIGTRPGD KDRLKLLAEA GLDVVVLDSS QGDSVYQIEF
IKWIKQTYPK IEIIAGNVVT REQAAQLIAA GADGLRIGMG SGSICITQEV MAVGRPQGTA
VYAVAEFASR FGIPCIADGG IGNIGHIAKA LALGASAVMM GGLLAGTTES PGEYFYHEGK
RVKVYRGMGS IEAMEHTQRG SASGKRSILN LDNAATARYF SEADAVKVAQ GVSGDVADKG
SINKFVPYLF TGLQHSFQDA GVKSVSELHS CARSGSLRFE LRTASAQLEG GVHGLNSYTK
RLFA
