IMDH_TOXGO
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 03-AUG-2022, entry version 91.
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;
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 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}.
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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; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 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 PANTHER; PTHR11911; PTHR11911; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; IMPDH; 2.
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 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 TgIMPDH-
FT 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
