IMDH_CRYPV
ID IMDH_CRYPV Reviewed; 400 AA.
AC Q8T6T2;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000303|PubMed:15269207};
DE Short=IMP dehydrogenase {ECO:0000303|PubMed:15269207};
DE Short=IMPD;
DE Short=IMPDH {ECO:0000303|PubMed:15269207};
DE EC=1.1.1.205 {ECO:0000269|PubMed:15269207};
GN ORFNames=56k.02, cgd6_20;
OS Cryptosporidium parvum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Cryptosporidiidae; Cryptosporidium.
OX NCBI_TaxID=5807;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Iowa;
RX PubMed=11959921; DOI=10.1073/pnas.092525699;
RA Striepen B., White M.W., Li C., Guerini M.N., Malik S.B., Logsdon J.M. Jr.,
RA Liu C., Abrahamsen M.S.;
RT "Genetic complementation in apicomplexan parasites.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6304-6309(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Iowa;
RX PubMed=12869580; DOI=10.1101/gr.1555203;
RA Bankier A.T., Spriggs H.F., Fartmann B., Konfortov B.A., Madera M.,
RA Vogel C., Teichmann S.A., Ivens A., Dear P.H.;
RT "Integrated mapping, chromosomal sequencing and sequence analysis of
RT Cryptosporidium parvum.";
RL Genome Res. 13:1787-1799(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=HNJ-1;
RA Yamagishi J., Wakaguri H., Sugano S., Kawano S., Fujisaki K., Sugimoto C.,
RA Watanabe J., Suzuki Y., Kimata I., Xuan X.;
RT "Construction and analysis of full-length cDNA library of Cryptosporidium
RT parvum.";
RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-11, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, ACTIVITY REGULATION, AND MASS SPECTROMETRY.
RX PubMed=15269207; DOI=10.1074/jbc.m407121200;
RA Umejiego N.N., Li C., Riera T., Hedstrom L., Striepen B.;
RT "Cryptosporidium parvum IMP dehydrogenase: identification of functional,
RT structural, and dynamic properties that can be exploited for drug design.";
RL J. Biol. Chem. 279:40320-40327(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS).
RX PubMed=20052976; DOI=10.1021/ja909947a;
RA Macpherson I.S., Kirubakaran S., Gorla S.K., Riera T.V., D'Aquino J.A.,
RA Zhang M., Cuny G.D., Hedstrom L.;
RT "The structural basis of Cryptosporidium-specific IMP dehydrogenase
RT inhibitor selectivity.";
RL J. Am. Chem. Soc. 132:1230-1231(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-89 OF 135-400 IN COMPLEX WITH
RP IMP.
RX PubMed=23668331; DOI=10.1021/jm400241j;
RA Gorla S.K., Kavitha M., Zhang M., Chin J.E., Liu X., Striepen B.,
RA Makowska-Grzyska M., Kim Y., Joachimiak A., Hedstrom L., Cuny G.D.;
RT "Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum
RT inosine 5'-monophosphate dehydrogenase.";
RL J. Med. Chem. 56:4028-4043(2013).
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:0000269|PubMed:15269207}.
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:0000269|PubMed:15269207};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P20839};
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. Resistant to mycophenolic acid (MPA) inhibition
CC (PubMed:15269207). {ECO:0000250|UniProtKB:P20839,
CC ECO:0000269|PubMed:15269207}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:15269207};
CC KM=150 uM for NAD(+) {ECO:0000269|PubMed:15269207};
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000305|PubMed:15269207}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:15269207}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P20839}.
CC -!- MASS SPECTROMETRY: Mass=42904; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:15269207};
CC -!- MISCELLANEOUS: Cryptosporidium IMPDH was acquired through lateral
CC transfer from eubacteria, and predictably the sensitivity to MPA
CC differs from that of mammalian IMPDH forms. This divergence of parasite
CC and host enzymes is exploited to design more potent parasite-specific
CC inhibitors. {ECO:0000305|PubMed:15269207}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000305}.
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DR EMBL; AF426177; AAL83208.1; -; Genomic_DNA.
DR EMBL; BX538350; CAD98604.1; -; Genomic_DNA.
DR EMBL; FX115298; BAJ77401.1; -; mRNA.
DR EMBL; FX115945; BAJ78048.1; -; mRNA.
DR PDB; 3FFS; X-ray; 3.19 A; A/B/C/D=1-400.
DR PDB; 4IXH; X-ray; 2.10 A; A/B/C/D=1-89, A/B/C/D=135-400.
DR PDB; 4QJ1; X-ray; 2.42 A; A/B/C/D=1-400.
DR PDB; 4RV8; X-ray; 2.05 A; A/B/C/D=1-89, A/B/C/D=135-400.
DR PDBsum; 3FFS; -.
DR PDBsum; 4IXH; -.
DR PDBsum; 4QJ1; -.
DR PDBsum; 4RV8; -.
DR AlphaFoldDB; Q8T6T2; -.
DR SMR; Q8T6T2; -.
DR BindingDB; Q8T6T2; -.
DR ChEMBL; CHEMBL6145; -.
DR VEuPathDB; CryptoDB:cgd6_20; -.
DR BRENDA; 1.1.1.205; 1728.
DR SABIO-RK; Q8T6T2; -.
DR UniPathway; UPA00601; UER00295.
DR EvolutionaryTrace; Q8T6T2; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 2.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005990; IMP_DH.
DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR PANTHER; PTHR11911; PTHR11911; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; GMP biosynthesis;
KW Metal-binding; NAD; Oxidoreductase; Potassium; Purine biosynthesis.
FT CHAIN 1..400
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000415682"
FT REGION 96..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..115
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 219
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT ACT_SITE 315
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKI7"
FT BINDING 163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 212..214
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 214
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:0000250|UniProtKB:P50097"
FT BINDING 216
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:0000250|UniProtKB:P50097"
FT BINDING 217
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:23668331"
FT BINDING 219
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:0000250|UniProtKB:P50097"
FT BINDING 252..254
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:23668331"
FT BINDING 275..276
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:23668331"
FT BINDING 299..303
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:23668331"
FT BINDING 329
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000269|PubMed:23668331"
FT BINDING 383
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 384
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT BINDING 385
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000250|UniProtKB:P50097"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 39..47
FT /evidence="ECO:0007829|PDB:4RV8"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 56..64
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:4IXH"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:4RV8"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:4QJ1"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 146..155
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:4QJ1"
FT HELIX 170..182
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 231..242
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 258..266
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 281..284
FT /evidence="ECO:0007829|PDB:4QJ1"
FT STRAND 288..291
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 294..300
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 305..309
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 341..358
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 364..370
FT /evidence="ECO:0007829|PDB:4RV8"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:4RV8"
FT HELIX 378..384
FT /evidence="ECO:0007829|PDB:4IXH"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:4IXH"
SQ SEQUENCE 400 AA; 43081 MW; DAAF96B44050DD18 CRC64;
MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM DTVTEHLMAV
GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST PDQNLDKEST DGKDTKSNNN
IDAYSNENLD NKGRLRVGAA IGVNEIERAK LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK
SKMNIDVIVG NVVTEEATKE LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS
VASKFGIPII ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR
GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG GLRSCMGYLG
SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK
