GMPR_LEIDB
ID GMPR_LEIDB Reviewed; 492 AA.
AC E9BDA8;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=GMP reductase {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|PubMed:7159467};
DE Short=GMPR {ECO:0000255|HAMAP-Rule:MF_03195};
DE EC=1.7.1.7 {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000269|PubMed:7159467};
DE AltName: Full=Guanosine 5'-monophosphate oxidoreductase {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|PubMed:7159467};
DE Short=Guanosine monophosphate reductase {ECO:0000255|HAMAP-Rule:MF_03195};
GN Name=GMPR {ECO:0000255|HAMAP-Rule:MF_03195}; ORFNames=LDBPK_170870;
OS Leishmania donovani (strain BPK282A1).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=981087;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=BPK282A1;
RA Downing T., Imamura H., Sanders M., Decuypere S., Hertz-Fowler C.,
RA Clark T.G., Rijal S., Sundar S., Quail M.A., De Doncker S., Maes I.,
RA Vanaerschot M., Stark O., Schonian G., Dujardin J.C., Berriman M.;
RT "Whole genome sequencing of Leishmania donovani clinical lines reveals
RT dynamic variation related to drug resistance.";
RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=7159467; DOI=10.1016/0006-2952(82)90307-0;
RA Spector T., Jones T.E.;
RT "Guanosine 5'-monophosphate reductase from Leishmania donovani. A possible
RT chemotherapeutic target.";
RL Biochem. Pharmacol. 31:3891-3897(1982).
CC -!- FUNCTION: Catalyzes the irreversible NADPH-dependent deamination of GMP
CC to IMP (PubMed:7159467). It functions in the conversion of nucleobase,
CC nucleoside and nucleotide derivatives of G to A nucleotides, and in
CC maintaining the intracellular balance of A and G nucleotides (By
CC similarity). {ECO:0000255|HAMAP-Rule:MF_03195,
CC ECO:0000269|PubMed:7159467}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=IMP + NADP(+) + NH4(+) = GMP + 2 H(+) + NADPH;
CC Xref=Rhea:RHEA:17185, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58053, ChEBI:CHEBI:58115,
CC ChEBI:CHEBI:58349; EC=1.7.1.7; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03195, ECO:0000269|PubMed:7159467};
CC -!- ACTIVITY REGULATION: Activated by GTP and inhibited by XMP and the IMP
CC analogs allopurinol nucleotide and thiopurinol nucleotide.
CC {ECO:0000269|PubMed:7159467}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for GMP {ECO:0000269|PubMed:7159467};
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03195}.
CC -!- SUBCELLULAR LOCATION: Glycosome {ECO:0000255|HAMAP-Rule:MF_03195}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03195}.
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DR EMBL; FR799604; CBZ33234.1; -; Genomic_DNA.
DR RefSeq; XP_003859941.1; XM_003859893.1.
DR AlphaFoldDB; E9BDA8; -.
DR SMR; E9BDA8; -.
DR PRIDE; E9BDA8; -.
DR EnsemblProtists; CBZ33234; CBZ33234; LDBPK_170870.
DR GeneID; 13393356; -.
DR KEGG; ldo:LDBPK_170870; -.
DR VEuPathDB; TriTrypDB:LdBPK_170870.1; -.
DR OMA; HDYHMTL; -.
DR PhylomeDB; E9BDA8; -.
DR SABIO-RK; E9BDA8; -.
DR Proteomes; UP000008980; Chromosome 17.
DR GO; GO:0020015; C:glycosome; IEA:UniProtKB-SubCell.
DR GO; GO:1902560; C:GMP reductase complex; IEA:InterPro.
DR GO; GO:0003920; F:GMP reductase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006144; P:purine nucleobase metabolic process; IEA:UniProtKB-KW.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00596; GMP_reduct_type1; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005993; GMPR.
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 1: Evidence at protein level;
KW CBS domain; Glycosome; GMP biosynthesis; Metal-binding; NAD; NADP;
KW Oxidoreductase; Peroxisome; Potassium; Purine biosynthesis;
KW Purine metabolism; Repeat.
FT CHAIN 1..492
FT /note="GMP reductase"
FT /id="PRO_0000433992"
FT DOMAIN 99..162
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT DOMAIN 164..223
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT MOTIF 490..492
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT ACT_SITE 319
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT ACT_SITE 321
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 30..31
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 78
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 260..262
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 313..314
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 314
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 316
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 319
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 322
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 352..354
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 375..376
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 401..403
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 402
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
FT BINDING 454..457
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03195"
SQ SEQUENCE 492 AA; 52011 MW; 852073775CB6C3B5 CRC64;
MAALGSLPTL PEGLTYDDVL LIPQRSPVRS RKAVNTSTRL SRNIHLKIPI VASNMDTVCE
DKTAVTMARE GGIGILHRFC SIEEQCAMVR KVKRAQSFLI EDPRMILPSA TKAEALEELN
WSGRKGGVSC LMVVDDFTSR RLCGVLSKSD LIFATDSALV ETLMTPVSRT VVSTNTAITL
EEAREVMRTK RTSNIPLLGP KGELLYLITQ SDILKLTGNR NATLDSRGRL IVGAAIGVKK
EDHKRAAALV DAGADVLVVD IAHGHSDLCI DMVKALKVNP LTNKVDIIAG NIATAEAAQD
LIDAGADGLK IGVGPGSICI TRLVAGSGVP QLSAVMDCAR VAKKHGVPCI ADGGVKTAGD
ICKAIAAGAD TVMLGNMLAG TDEAPGRVLV KDGKKVKIIR GMAGFGANIS KAEREKRLDE
DVFNDLVPEG VEGSVPCKGP LAPILKQLVG GLRSGISYCG SHSIADMQQR ARFVRMSGAG
LRESGSHDIS KL
