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 24-JAN-2024, 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}; 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; 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. {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE017341; AAW40949.1; -; Genomic_DNA. DR RefSeq; XP_566768.1; XM_566768.1. DR AlphaFoldDB; Q5KP44; -. DR SMR; Q5KP44; -. DR STRING; 214684.Q5KP44; -. DR BindingDB; Q5KP44; -. DR ChEMBL; CHEMBL4295605; -. DR PaxDb; 214684-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; 166969at2759; -. 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; 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 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 //