IMDH_PNECA
ID IMDH_PNECA Reviewed; 529 AA.
AC Q12658; Q9UVL0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 2.
DT 03-AUG-2022, entry version 114.
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=GUA1;
OS Pneumocystis carinii.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Pneumocystidomycetes; Pneumocystidaceae; Pneumocystis.
OX NCBI_TaxID=4754;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 119-132;
RP 172-186 AND 300-313, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=8980752; DOI=10.1128/aac.41.1.40;
RA O'Gara M.J., Lee C.H., Weinberg G.A., Nott J.M., Queener S.F.;
RT "IMP dehydrogenase from Pneumocystis carinii as a potential drug target.";
RL Antimicrob. Agents Chemother. 41:40-48(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND FUNCTION.
RX PubMed=11223253; DOI=10.1016/s0378-1119(00)00577-1;
RA Ye D., Lee C.H., Queener S.F.;
RT "Differential splicing of Pneumocystis carinii f. sp. carinii inosine 5'-
RT monophosphate dehydrogenase pre-mRNA.";
RL Gene 263:151-158(2001).
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:11223253,
CC ECO:0000269|PubMed:8980752}.
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. MPA is a potent inhibitor in culture.
CC {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:8980752}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.7 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:8980752};
CC KM=314 uM for NAD(+) {ECO:0000269|PubMed:8980752};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q12658-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12658-2; Sequence=VSP_042318;
CC -!- PTM: The N-terminus is blocked.
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; U42442; AAA97462.1; -; mRNA.
DR EMBL; AF196975; AAF13230.1; -; mRNA.
DR AlphaFoldDB; Q12658; -.
DR SMR; Q12658; -.
DR PRIDE; Q12658; -.
DR BRENDA; 1.1.1.205; 4924.
DR SABIO-RK; Q12658; -.
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; 1.
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 1: Evidence at protein level;
KW Alternative splicing; CBS domain; Cytoplasm; Direct protein sequencing;
KW GMP biosynthesis; Metal-binding; NAD; Oxidoreductase; Potassium;
KW Purine biosynthesis; Repeat.
FT CHAIN 1..529
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093679"
FT DOMAIN 124..185
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 187..243
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 338
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 443
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 281..283
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 331..333
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
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 335
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 336
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 338
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 371..373
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 394..395
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 418..422
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 455
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 514
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 515
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 1..75
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11223253,
FT ECO:0000303|PubMed:8980752"
FT /id="VSP_042318"
FT CONFLICT 187
FT /note="M -> I (in Ref. 1; AAA97462)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="A -> Q (in Ref. 1; AAA97462)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="I -> N (in Ref. 1; AAA97462)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 529 AA; 58066 MW; 030573A8854ADB5A CRC64;
MGEDSYLCLS EEIKKKLEEY SEKDGYDLDS LICSRRHGGL TYNDIIILPG YIDFEVNSVS
LESHITKKIV LKTPFMSSPM DTVTESDMAI NLALLGGIGV IHHNCTIEEQ TEMVRKVKKF
ENGFITSPIV LSLNHRVRDV RRIKEELGFS GIPITDTGQL NGKLLGIVTS RDIQFHNNDE
SFLSEVMTKD LVTGSEGIRL EEANEILRSC KKGKLPIVDK EGNLTALLSR SDLMKNLHFP
LASKLPDSKQ LICAAAVGTR PDDRIRLKHL VEAGLDIVVL DSSQGNSIYQ INMIKWIKKE
FPNLEVIAGN VVTREQAANL ISAGADALRV GMGSGSICIT QEIMAVGRPQ ATAVYAVSEF
ASKFGVPTIA DGGIENIGHI TKALALGASA VMMGNLLAGT TESPGQYYYR DGQRLKSYRG
MGSIDAMEHL SGKNKGDNAA SSRYFGEADT IRVAQGVSGS VIDKGSLHVY VPYLRTGLQH
SLQDIGVQNL TELRKQVKEK NIRFEFRTVA SQLEGNVHGL DSYQKKLWS
