MPAF_PENBR
ID MPAF_PENBR Reviewed; 527 AA.
AC F1DBB2;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 50.
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:21398490};
GN Name=mpaF {ECO:0000303|PubMed:21398490};
OS Penicillium brevicompactum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5074 {ECO:0000312|EMBL:ADY00133.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=IBT 23078;
RX PubMed=21398490; DOI=10.1128/aem.03015-10;
RA Regueira T.B., Kildegaard K.R., Hansen B.G., Mortensen U.H., Hertweck C.,
RA Nielsen J.;
RT "Molecular basis for mycophenolic acid biosynthesis in Penicillium
RT brevicompactum.";
RL Appl. Environ. Microbiol. 77:3035-3043(2011).
RN [2]
RP FUNCTION.
RX PubMed=21923907; DOI=10.1186/1471-2180-11-202;
RA Hansen B.G., Genee H.J., Kaas C.S., Nielsen J.B., Regueira T.B.,
RA Mortensen U.H., Frisvad J.C., Patil K.R.;
RT "A new class of IMP dehydrogenase with a role in self-resistance of
RT mycophenolic acid producing fungi.";
RL BMC Microbiol. 11:202-202(2011).
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 (PubMed:21398490). Does not play a role in the
CC biosynthesis of MPA, but is involved in self resistance to MPA, since
CC MPA acts as an inhibitor of IMP dehydrogenases (PubMed:21923907).
CC {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:21398490,
CC ECO:0000269|PubMed:21923907}.
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; HQ731031; ADY00133.1; -; Genomic_DNA.
DR AlphaFoldDB; F1DBB2; -.
DR SMR; F1DBB2; -.
DR BRENDA; 1.1.1.205; 4601.
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; IDA: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; 2.
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..527
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000436574"
FT DOMAIN 121..183
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 184..240
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT REGION 506..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 334
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 440
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 277..279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 327..329
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 329
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 331
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 332
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 334
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 367..369
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 390..391
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 452
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 511
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 512
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 527 AA; 55937 MW; AA1837B38F47674A CRC64;
MVEILDYTKA LEVLKEYPSG DGLHVDTLLD SDNHGALTYN DFLILPGSIT FSAADVSLDT
KVTRRFTIKA PLLSSPMDTV TEHNMAIHMA LLGGLGVIHN NCPPDDQAEM VRKVKRYENG
FILDPVVLSP STTVAEAKEL KTKWNFGGFP VTEKGTLHSK LLGIVTSRDI QFHKTPEDPV
TAVMSTDLVT APAGTTLAEA NEVLRSSKKG KLPIVDKDGL LVSLLSRSDL MKNIHYPLAS
KLPSKQLLCA AAISTHDADK VRLQKLVDAG LDIVVVDSSQ GNSMYQIAMI KWIKSTFPDI
DIIAGNIVTR EQAAALIAAG ADGLRIGMGS GSACITQEVM AVGRPQAASV RSVSAFAARF
GVPTIADGGV QNLGHIVKGL ALGASAVMMG SLLAGTTESP GEYYVSNEGQ LVKAFRGMGS
IAVMEDKGKS GGGKNAGASR YFSENDKVKV AQGVAGSVVD RGSITQYVPY LVAGIQHSLQ
DIGVQDLEAL HTGVNNGQVR FEMRSASAQT EGNVHGLHSH EKKLYSS
