GMPR_LEIMA
ID GMPR_LEIMA Reviewed; 492 AA.
AC Q4QEB3;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=GMP reductase {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|Ref.2};
DE Short=GMPR {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|Ref.2};
DE EC=1.7.1.7 {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000269|Ref.2};
DE AltName: Full=Guanosine 5'-monophosphate oxidoreductase {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|Ref.2};
DE Short=Guanosine monophosphate reductase {ECO:0000255|HAMAP-Rule:MF_03195};
GN Name=GMPR {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000303|Ref.2};
GN ORFNames=LMJF_17_0725;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/IL/81/Friedlin;
RX PubMed=16020728; DOI=10.1126/science.1112680;
RA Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G.,
RA Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A.,
RA Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M.,
RA Bianchettin G., Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E.,
RA Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M.,
RA De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N.,
RA Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A.,
RA Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S.,
RA Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M.,
RA Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S.,
RA Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M.,
RA Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E.,
RA Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C.,
RA Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K.,
RA Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V.,
RA Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J.,
RA Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D.,
RA Barrell B.G., Myler P.J.;
RT "The genome of the kinetoplastid parasite, Leishmania major.";
RL Science 309:436-442(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RA Smith S.A.;
RT "Characterization of a novel Leishmania guanosine 5'-monophosphate
RT reductase.";
RL Thesis (2006), McGill University / Montreal, Canada.
CC -!- FUNCTION: Catalyzes the irreversible NADPH-dependent deamination of GMP
CC to IMP. It functions in the conversion of nucleobase, nucleoside and
CC nucleotide derivatives of G to A nucleotides, and in maintaining the
CC intracellular balance of A and G nucleotides. {ECO:0000255|HAMAP-
CC Rule:MF_03195, ECO:0000269|Ref.2}.
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|Ref.2};
CC -!- ACTIVITY REGULATION: Activated by GTP and inhibited by ATP and IMP.
CC Mycophenolic acid (MPA) is a competitive inhibitor of the enzyme with
CC respect to NADPH. {ECO:0000269|Ref.2}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37 uM for GMP {ECO:0000269|Ref.2};
CC KM=12 uM for NADPH {ECO:0000269|Ref.2};
CC Note=kcat is 0.059 min(-1) with GMP as substrate and 0.043 min(-1)
CC with NADPH as substrate. {ECO:0000269|Ref.2};
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAJ03667.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305|Ref.2};
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DR EMBL; FR796413; CAJ03667.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_001682335.1; XM_001682283.1.
DR AlphaFoldDB; Q4QEB3; -.
DR SMR; Q4QEB3; -.
DR STRING; 5664.LmjF.17.0725; -.
DR EnsemblProtists; CAJ03667; CAJ03667; LMJF_17_0725.
DR GeneID; 5650809; -.
DR KEGG; lma:LMJF_17_0725; -.
DR VEuPathDB; TriTrypDB:LmjF.17.0725; -.
DR VEuPathDB; TriTrypDB:LMJLV39_170014800; -.
DR VEuPathDB; TriTrypDB:LMJSD75_170014400; -.
DR eggNOG; KOG2550; Eukaryota.
DR HOGENOM; CLU_022552_2_1_1; -.
DR InParanoid; Q4QEB3; -.
DR BRENDA; 1.7.1.7; 2950.
DR Proteomes; UP000000542; Chromosome 17.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0020015; C:glycosome; ISO:GeneDB.
DR GO; GO:1902560; C:GMP reductase complex; IEA:InterPro.
DR GO; GO:0005730; C:nucleolus; ISO:GeneDB.
DR GO; GO:0003920; F:GMP reductase activity; ISO:GeneDB.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
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; Metal-binding; NADP; Oxidoreductase; Peroxisome;
KW Potassium; Purine metabolism; Reference proteome; Repeat.
FT CHAIN 1..492
FT /note="GMP reductase"
FT /id="PRO_0000433991"
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; 52032 MW; 2B3F712BBC005CCE CRC64;
MAALGSLPTL PEGLTYDDVL LIPQRSPVRS RKAVNTSTRL SRNIHLKIPI VASNMDTVCE
DKTAVTMARE GGIGILHRFC SIEEQCAMVR KVKRAQSFLI EDPRMILPSA TKAEALEELN
WSGRKGGVSC LMVVDDLTSR RLCGVLTKSD LTFATGSALV ETLMTPVSRM VVSTNTAITL
EEAREVMRTK RTKNIPLLGP KGELLYLITR SDILKLTGNL NATLDSRGRL IVGAAIGVKK
EDHERAAALV DAGADVLVVD IAHGHSDLCI DMVKALKVNP LTNKVDIIAG NIATAEAAQD
LIDAGADGLK IGVGPGSICI TRLVAGSGVP QLSSVMDCAR VAKKHGVPCI ADGGIKTAGD
ICKAIAAGAD TVMLGNMLAG TDEAPGRVLV KDGKKVKIIR GMAGFGANIS KAEREQRLDE
DVFHDLVPEG VEGSVPCKGP LAPILKQLVG GLRSGISYCG SHSIADMQQR ARFVRMSGAG
LRESGSHDIS KL
