ID IMDH_TOXGO Reviewed; 551 AA. AC Q4VRV8; Q4VRV6; DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2005, sequence version 1. DT 13-SEP-2023, entry version 94. 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 Toxoplasma gondii. OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia; OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma. OX NCBI_TaxID=5811; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TGIMPDH AND TGIMPDH-S), FUNCTION, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND ACTIVITY RP REGULATION. RC STRAIN=RH; RX PubMed=15917510; DOI=10.1128/aac.49.6.2172-2179.2005; RA Sullivan W.J. Jr., Dixon S.E., Li C., Striepen B., Queener S.F.; RT "IMP dehydrogenase from the protozoan parasite Toxoplasma gondii."; RL Antimicrob. Agents Chemother. 49:2172-2179(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, ECO:0000269|PubMed:15917510}. 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 and adenine dinucleotide CC analogs such as thiazole-4-carboxamide adenine dinucleotide (TAD). CC {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:15917510}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=144 uM for NAD(+) {ECO:0000269|PubMed:15917510}; 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 ECO:0000269|PubMed:15917510}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=TgIMPDH; CC IsoId=Q4VRV8-1; Sequence=Displayed; CC Name=TgIMPDH-S; CC IsoId=Q4VRV8-2; Sequence=VSP_042319; CC -!- MISCELLANEOUS: [Isoform TgIMPDH-S]: Lacks the active-site flap. CC {ECO:0000305}. 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; AY663109; AAV73841.1; -; mRNA. DR EMBL; AY661469; AAV74388.1; -; mRNA. DR AlphaFoldDB; Q4VRV8; -. DR SMR; Q4VRV8; -. DR VEuPathDB; ToxoDB:TGARI_233110; -. DR VEuPathDB; ToxoDB:TGCAST_233110; -. DR VEuPathDB; ToxoDB:TGCOUG_233110A; -. DR VEuPathDB; ToxoDB:TGDOM2_233110; -. DR VEuPathDB; ToxoDB:TGFOU_233110; -. DR VEuPathDB; ToxoDB:TGGT1_233110; -. DR VEuPathDB; ToxoDB:TGMAS_233110; -. DR VEuPathDB; ToxoDB:TGME49_233110; -. DR VEuPathDB; ToxoDB:TGP89_233110A; -. DR VEuPathDB; ToxoDB:TGPRC2_426780; -. DR VEuPathDB; ToxoDB:TGRH88_077080; -. DR VEuPathDB; ToxoDB:TGRUB_233110; -. DR VEuPathDB; ToxoDB:TGVAND_233110; -. DR VEuPathDB; ToxoDB:TGVEG_233110; -. DR BRENDA; 1.1.1.205; 6411. DR SABIO-RK; Q4VRV8; -. 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; cd04601; CBS_pair_IMPDH; 1. DR CDD; cd00381; IMPDH; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 2. 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; 2. 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 Alternative splicing; CBS domain; Cytoplasm; GMP biosynthesis; KW Metal-binding; NAD; Oxidoreductase; Potassium; Purine biosynthesis; Repeat. FT CHAIN 1..551 FT /note="Inosine-5'-monophosphate dehydrogenase" FT /id="PRO_0000415683" FT DOMAIN 102..163 FT /note="CBS 1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT DOMAIN 165..221 FT /note="CBS 2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT REGION 407..462 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 425..462 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 315 FT /note="Thioimidate intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT ACT_SITE 465 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 258..260 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 308..310 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 310 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 312 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 313 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 315 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 349..351 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 372..373 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 396..400 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 477 FT /ligand="IMP" FT /ligand_id="ChEBI:CHEBI:58053" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156" FT BINDING 536 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 537 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 VAR_SEQ 361..551 FT /note="ALALGANAVMMGSMLAGTEEAPGEYYFHNGVRVKTYRGMGSLDAMRAGTRRT FT ASPPARGLRSPEASPSTAASSGGASRASALSEASPSAKSEASRTSTSTGSAARYFAENQ FT TIRVAQGVSGCVVDKGTVMQLIPYVIQGVKHGMQDIGARTLRDLHAQLVGGELRFDVRS FT GAAQREGDVHDLHSFERKLYA -> VWRCAEGRRCS (in isoform FT TgIMPDH-S)" FT /evidence="ECO:0000303|PubMed:15917510" FT /id="VSP_042319" SQ SEQUENCE 551 AA; 59047 MW; 788A1DAC369E3DE9 CRC64; MADGWDAEKI FNTTVFGFTY DDLILMPGHI DFGVNDVDLS TRITRNLHVR TPIVSSPMDT VTEHRMAIGC ALMGGMGVIH NNMETARQVA EVQKVKRYEN GFILDPFVLR PSDSVADVYR IKEKYGYSSV PITDTGMLGG KLLGIVTSRD IDFLTDVHTP LSEVMTSDLV VGHEPVQLAE ANELLRESKK GKLPIVNDNF ELVALISRND LKKNREFPLA SKDSNKQLLV GAAVSTKPHD IERAKALQEA GADVLVVDSS QGDSIYQVDL VKRLKAAFPE LQIIGGNVVT ARQAKSLIDA GVDGLRIGMG SGSICTTQVV CAVGRAQATA VYHVCKYARE HGDVPCIADG GIQNSGHVMK ALALGANAVM MGSMLAGTEE APGEYYFHNG VRVKTYRGMG SLDAMRAGTR RTASPPARGL RSPEASPSTA ASSGGASRAS ALSEASPSAK SEASRTSTST GSAARYFAEN QTIRVAQGVS GCVVDKGTVM QLIPYVIQGV KHGMQDIGAR TLRDLHAQLV GGELRFDVRS GAAQREGDVH DLHSFERKLY A //