MPAF2_PENBR
ID MPAF2_PENBR Reviewed; 548 AA.
AC A0A0B5L585;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 32.
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};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein F' {ECO:0000303|PubMed:25630520};
GN Name=mpaF' {ECO:0000303|PubMed:25630520};
OS Penicillium brevicompactum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5074;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NRRL864;
RX PubMed=25630520; DOI=10.1002/cbic.201402600;
RA Zhang W., Cao S., Qiu L., Qi F., Li Z., Yang Y., Huang S., Bai F., Liu C.,
RA Wan X., Li S.;
RT "Functional characterization of MpaG', the O-methyltransferase involved in
RT the biosynthesis of mycophenolic acid.";
RL ChemBioChem 16:565-569(2015).
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 (By
CC similarity). Part of the gene cluster that mediates the biosynthesis of
CC mycophenolic acid (MPA), the first isolated antibiotic natural product
CC in the world (By similarity). Does not play a role in the biosynthesis
CC of MPA, but is involved in self resistance to MPA, since MPA acts as an
CC inhibitor of IMP dehydrogenases (By similarity).
CC {ECO:0000250|UniProtKB:W6QIT2, 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; KM595305; AJG44383.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0B5L585; -.
DR SMR; A0A0B5L585; -.
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 GO; GO:0140729; P:self-resistance to endogenously produced metabolite; ISS: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; 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 3: Inferred from homology;
KW CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD;
KW Oxidoreductase; Potassium; Purine biosynthesis; Repeat.
FT CHAIN 1..548
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000451893"
FT DOMAIN 121..201
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 205..261
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 527..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 355
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 461
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 298..300
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 348..350
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 350
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 352
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 353
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 355
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 388..390
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 411..412
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 473
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 528
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 548 AA; 58191 MW; 4DC00B2E4E90519C CRC64;
MVEILDYTKA LEVLKEYPSG DGLHVDTLLD SDNHGALTYN DFLILPGSIT FSAADVSLDT
KVTRRFTIKA PLLSSPMDTV TEHNMAIHMA LLGGLGVIHN NCPPDDQAEM VRKVKRYENG
FILDPVVLSP STTVAEAKEL KTKWNFGGFP VTGKTHYLSS FGKLASSDSF SLLEKGTLHS
KLLGIVTSRD IQFHKTPEDP VTAVMSTELV TAPAGTTLAE ANEVLRSSKK GKLPIVDKDG
LLVSLLSRSD LMKNIHYPLA SKLPSKQLLC AAAISTHDAD KVRLQKLVDA GLDIVVVDSS
QGNSMYQIAM IKWIKSTFPD IDIIAGNIVT REQAAALIAA GADGLRIGMG SGSACITQEV
MAVGRPQAAS VRSVSAFAAR FGVPTIADGG VQNLGHIVKG LALGASAVMM GSLLAGTTES
PGEYYVSNEG QLVKAFRGMG SIAVMEDKGK SGGGKNAGAS RYFSENDKVK VAQGVAGSVV
DRGSITQYVP YLVAGIQHSL QDIGVQDLEA LHNGVNNGQV RFEMRSASAQ TEGNVHGLHS
HEKKLYSS
