PGFS_LEIMA
ID PGFS_LEIMA Reviewed; 284 AA.
AC P22045; Q4Q646;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=9,11-endoperoxide prostaglandin H2 reductase {ECO:0000303|PubMed:12633659};
DE EC=1.1.1.- {ECO:0000269|PubMed:12633659};
DE AltName: Full=Prostaglandin F2-alpha synthase;
GN Name=P100/11E;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2918000; DOI=10.1016/s0021-9258(19)84990-6;
RA Samaras N., Spithill T.W.;
RT "The developmentally regulated P100/11E gene of Leishmania major shows
RT homology to a superfamily of reductase genes.";
RL J. Biol. Chem. 264:4251-4254(1989).
RN [2]
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 [3]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=MHOM/SU/73/5ASKH;
RX PubMed=12633659; DOI=10.1016/s0020-7519(02)00254-0;
RA Kabututu Z., Martin S.K., Nozaki T., Kawazu S., Okada T., Munday C.J.,
RA Duszenko M., Lazarus M., Thuita L.W., Urade Y., Kubata B.K.;
RT "Prostaglandin production from arachidonic acid and evidence for a 9,11-
RT endoperoxide prostaglandin H2 reductase in Leishmania.";
RL Int. J. Parasitol. 33:221-228(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RC STRAIN=MHOM/IL/81/Friedlin;
RG Seattle structural genomics center for infectious disease (SSGCID);
RT "X-ray crystal structure of apo prostaglandin F synthase from Leishmania
RT major Friedlin.";
RL Submitted (JUN-2012) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the NADP-dependent formation of prostaglandin F2-
CC alpha from prostaglandin H2. Has also aldo/ketoreductase activity
CC toward the synthetic substrates 9,10-phenanthrenequinone and p-
CC nitrobenzaldehyde. {ECO:0000269|PubMed:12633659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin
CC H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:12633659};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for prostaglandin H2 {ECO:0000269|PubMed:12633659};
CC KM=12.5 uM for 9,10-phenanthrenequinone
CC {ECO:0000269|PubMed:12633659};
CC KM=12.8 uM for p-nitrobenzaldehyde {ECO:0000269|PubMed:12633659};
CC KM=3 uM for NADPH {ECO:0000269|PubMed:12633659};
CC Vmax=270 nmol/min/mg enzyme toward prostaglandin H2
CC {ECO:0000269|PubMed:12633659};
CC Vmax=4780 nmol/min/mg enzyme toward 9,10-phenanthrenequinone
CC {ECO:0000269|PubMed:12633659};
CC Vmax=7280 nmol/min/mg enzyme toward p-nitrobenzaldehyde
CC {ECO:0000269|PubMed:12633659};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12633659}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12633659}.
CC -!- DEVELOPMENTAL STAGE: P110/11E abundance is markedly elevated in
CC promastigotes relative to amastigotes.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; J04483; AAA57350.1; -; mRNA.
DR EMBL; FR796427; CAJ08404.1; -; Genomic_DNA.
DR PIR; A32950; A32950.
DR RefSeq; XP_001685202.1; XM_001685150.1.
DR PDB; 4F40; X-ray; 1.60 A; A/B=1-284.
DR PDB; 4G5D; X-ray; 1.80 A; A/B=1-284.
DR PDBsum; 4F40; -.
DR PDBsum; 4G5D; -.
DR AlphaFoldDB; P22045; -.
DR SMR; P22045; -.
DR STRING; 5664.LmjF.31.2150; -.
DR EnsemblProtists; CAJ08404; CAJ08404; LMJF_31_2150.
DR GeneID; 5654147; -.
DR KEGG; lma:LMJF_31_2150; -.
DR VEuPathDB; TriTrypDB:LmjF.31.2150; -.
DR VEuPathDB; TriTrypDB:LMJLV39_310030400; -.
DR VEuPathDB; TriTrypDB:LMJSD75_310030400; -.
DR eggNOG; KOG1577; Eukaryota.
DR InParanoid; P22045; -.
DR OMA; AFKPGNE; -.
DR BRENDA; 1.1.1.188; 2950.
DR SABIO-RK; P22045; -.
DR UniPathway; UPA00662; -.
DR Proteomes; UP000000542; Chromosome 31.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0036130; F:prostaglandin H2 endoperoxidase reductase activity; IEA:RHEA.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd19156; AKR_AKR5A1_2; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044499; AKR5A.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR PANTHER; PTHR43827; PTHR43827; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; NADP; Nucleotide-binding;
KW Oxidoreductase; Prostaglandin biosynthesis; Prostaglandin metabolism;
KW Reference proteome.
FT CHAIN 1..284
FT /note="9,11-endoperoxide prostaglandin H2 reductase"
FT /id="PRO_0000124653"
FT ACT_SITE 54
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 24..25
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 49
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 149..150
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 197..202
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 240..242
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 246..250
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 79
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT CONFLICT 38
FT /note="K -> N (in Ref. 1; AAA57350)"
FT /evidence="ECO:0000305"
FT TURN 4..6
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 16..20
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 31..42
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 87..101
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 117..123
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 142..150
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 153..160
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 181..189
FT /evidence="ECO:0007829|PDB:4F40"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:4G5D"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 209..217
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 244..251
FT /evidence="ECO:0007829|PDB:4F40"
FT HELIX 260..267
FT /evidence="ECO:0007829|PDB:4F40"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:4F40"
SQ SEQUENCE 284 AA; 31850 MW; D2FF5967F7EDC767 CRC64;
MAGVDKAMVT LSNGVKMPQF GLGVWQSPAG EVTENAVKWA LCAGYRHIDT AAIYKNEESV
GAGLRASGVP REDVFITTKL WNTEQGYEST LAAFEESRQK LGVDYIDLYL IHWPRGKDIL
SKEGKKYLDS WRAFEQLYKE KKVRAIGVSN FHIHHLEDVL AMCTVTPMVN QVELHPLNNQ
ADLRAFCDAK QIKVEAWSPL GQGKLLSNPI LSAIGAKYNK TAAQVILRWN IQKNLITIPK
SVHRERIEEN ADIFDFELGA EDVMSIDALN TNSRYGPDPD EAQF
