PLM2_PLAFX
ID PLM2_PLAFX Reviewed; 453 AA.
AC P46925; A0A0L7K5Z5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Plasmepsin II {ECO:0000303|PubMed:9169469};
DE Short=PLM II {ECO:0000303|PubMed:8816746};
DE EC=3.4.23.39 {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:15574427, ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843, ECO:0000269|PubMed:26670264, ECO:0000269|PubMed:8816746, ECO:0000269|PubMed:8844673};
DE AltName: Full=Aspartic hemoglobinase II {ECO:0000303|PubMed:7935597};
DE AltName: Full=PfAPD {ECO:0000303|PubMed:7935597};
DE AltName: Full=PfPM1 {ECO:0000303|PubMed:19271776};
DE AltName: Full=Plasmepsin 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=PMII {ECO:0000303|PubMed:9169469};
OS Plasmodium falciparum (isolate HB3).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=137071 {ECO:0000312|Proteomes:UP000054289};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, AND
RP 3D-STRUCTURE MODELING.
RC STRAIN=HB3;
RX PubMed=7935597; DOI=10.1016/0166-6851(94)90024-8;
RA Dame J.B., Reddy G.R., Yowell C.A., Dunn B.M., Kay J., Berry C.;
RT "Sequence, expression and modeled structure of an aspartic proteinase from
RT the human malaria parasite Plasmodium falciparum.";
RL Mol. Biochem. Parasitol. 64:177-190(1994).
RN [2] {ECO:0000312|Proteomes:UP000054289}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HB3 {ECO:0000312|Proteomes:UP000054289};
RG The Broad Institute Genome Sequencing Platform;
RA Volkman S.K., Neafsey D.E., Dash A.P., Chitnis C.E., Hartl D.L.,
RA Young S.K., Zeng Q., Koehrsen M., Alvarado L., Berlin A., Borenstein D.,
RA Chapman S.B., Chen Z., Engels R., Freedman E., Gellesch M., Goldberg J.,
RA Griggs A., Gujja S., Heilman E.R., Heiman D.I., Howarth C., Jen D.,
RA Larson L., Mehta T., Neiman D., Park D., Pearson M., Roberts A., Saif S.,
RA Shea T., Shenoy N., Sisk P., Stolte C., Sykes S., Walk T., White J.,
RA Yandava C., Haas B., Henn M.R., Nusbaum C., Birren B.;
RT "Annotation of Plasmodium falciparum HB3.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=8844673; DOI=10.1016/0166-6851(96)02651-5;
RA Luker K.E., Francis S.E., Gluzman I.Y., Goldberg D.E.;
RT "Kinetic analysis of plasmepsins I and II aspartic proteases of the
RT Plasmodium falciparum digestive vacuole.";
RL Mol. Biochem. Parasitol. 79:71-78(1996).
RN [4]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PROTEOLYTIC CLEAVAGE, AND LACK
RP OF GLYCOSYLATION.
RX PubMed=9169469; DOI=10.1074/jbc.272.23.14961;
RA Francis S.E., Banerjee R., Goldberg D.E.;
RT "Biosynthesis and maturation of the malaria aspartic hemoglobinases
RT plasmepsins I and II.";
RL J. Biol. Chem. 272:14961-14968(1997).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=11782538; DOI=10.1073/pnas.022630099;
RA Banerjee R., Liu J., Beatty W., Pelosof L., Klemba M., Goldberg D.E.;
RT "Four plasmepsins are active in the Plasmodium falciparum food vacuole,
RT including a protease with an active-site histidine.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:990-995(2002).
RN [6]
RP DEVELOPMENTAL STAGE, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=12850260; DOI=10.1016/s0166-6851(03)00119-1;
RA Banerjee R., Francis S.E., Goldberg D.E.;
RT "Food vacuole plasmepsins are processed at a conserved site by an acidic
RT convertase activity in Plasmodium falciparum.";
RL Mol. Biochem. Parasitol. 129:157-165(2003).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ALA-241 AND PHE-244.
RX PubMed=15574427; DOI=10.1074/jbc.m412086200;
RA Istvan E.S., Goldberg D.E.;
RT "Distal substrate interactions enhance plasmepsin activity.";
RL J. Biol. Chem. 280:6890-6896(2005).
RN [8] {ECO:0007744|PDB:1SME}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 125-453, CATALYTIC ACTIVITY, AND
RP DISULFIDE BONDS.
RX PubMed=8816746; DOI=10.1073/pnas.93.19.10034;
RA Silva A.M., Lee A.Y., Gulnik S.V., Maier P., Collins J., Bhat T.N.,
RA Collins P.J., Cachau R.E., Luker K.E., Gluzman I.Y., Francis S.E.,
RA Oksman A., Goldberg D.E., Erickson J.W.;
RT "Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme
RT from Plasmodium falciparum.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10034-10039(1996).
RN [9] {ECO:0007744|PDB:1PFZ}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 75-453, AND DISULFIDE BONDS.
RX PubMed=9886289; DOI=10.1038/4905;
RA Bernstein N.K., Cherney M.M., Loetscher H., Ridley R.G., James M.N.;
RT "Crystal structure of the novel aspartic proteinase zymogen proplasmepsin
RT II from Plasmodium falciparum.";
RL Nat. Struct. Biol. 6:32-37(1999).
RN [10] {ECO:0007744|PDB:1LEE, ECO:0007744|PDB:1LF2}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 123-453 OF MUTANT SER-330 IN
RP COMPLEX WITH INHIBITOR, AND DISULFIDE BONDS.
RX PubMed=12454457; DOI=10.1107/s0907444902014695;
RA Asojo O.A., Afonina E., Gulnik S.V., Yu B., Erickson J.W., Randad R.,
RA Medjahed D., Silva A.M.;
RT "Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at
RT 1.8 A in complex with the inhibitors rs367 and rs370.";
RL Acta Crystallogr. D 58:2001-2008(2002).
RN [11] {ECO:0007744|PDB:1M43}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 123-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RA Asojo O.A., Silva A.M., Gulnik S.;
RT "Novel uncomplexed and complex structures of PM II, an aspartic protease
RT from P. falciparum.";
RL Submitted (JUL-2002) to the PDB data bank.
RN [12] {ECO:0007744|PDB:1ME6}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RA Freire E., Nezami A.G., Amzel L.M.;
RT "CRYSTAL STRUCTURE OF PLASMEPSIN II, AN ASPARTYL PROTEASE FROM PLASMODIUM
RT FALCIPARUM, IN COMPLEX WITH A STATINE-BASED INHIBITOR.";
RL Submitted (AUG-2002) to the PDB data bank.
RN [13] {ECO:0007744|PDB:1LF3, ECO:0007744|PDB:1LF4}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 123-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RX PubMed=12614616; DOI=10.1016/s0022-2836(03)00036-6;
RA Asojo O.A., Gulnik S.V., Afonina E., Yu B., Ellman J.A., Haque T.S.,
RA Silva A.M.;
RT "Novel uncomplexed and complexed structures of plasmepsin II, an aspartic
RT protease from Plasmodium falciparum.";
RL J. Mol. Biol. 327:173-181(2003).
RN [14] {ECO:0007744|PDB:1W6H, ECO:0007744|PDB:1W6I}
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 123-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RA Lindberg J., Johansson P.-O., Rosenquist A., Kvarnstroem I., Vrang L.,
RA Samuelsson B., Unge T.;
RT "Structural Study of a Novel Inhibitor with Bulky P1 Side Chain in Complex
RT with Plasmepsin II -Implications for Drug Design.";
RL Submitted (AUG-2004) to the PDB data bank.
RN [15] {ECO:0007744|PDB:1XDH}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 123-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RA Prade L.;
RT "Structure of plasmepsin II in complex with pepstatin A.";
RL Submitted (SEP-2004) to the PDB data bank.
RN [16] {ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RA Prade L.;
RT "Structure of plasmepsin II in complex of an pepstatin analogue.";
RL Submitted (SEP-2004) to the PDB data bank.
RN [17] {ECO:0007744|PDB:2BJU}
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) IN COMPLEX WITH INHIBITOR, AND
RP DISULFIDE BONDS.
RX PubMed=15840589; DOI=10.1074/jbc.m501519200;
RA Prade L., Jones A.F., Boss C., Richard-Bildstein S., Meyer S., Binkert C.,
RA Bur D.;
RT "X-ray structure of plasmepsin II complexed with a potent achiral
RT inhibitor.";
RL J. Biol. Chem. 280:23837-23843(2005).
RN [18] {ECO:0007744|PDB:2IGX, ECO:0007744|PDB:2IGY}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, AND DISULFIDE BONDS.
RX PubMed=17091526; DOI=10.1002/cmdc.200600223;
RA Boss C., Corminboeuf O., Grisostomi C., Meyer S., Jones A.F., Prade L.,
RA Binkert C., Fischli W., Weller T., Bur D.;
RT "Achiral, cheap, and potent inhibitors of Plasmepsins I, II, and IV.";
RL ChemMedChem 1:1341-1345(2006).
RN [19] {ECO:0007744|PDB:3F9Q}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 125-453, AND DISULFIDE BONDS.
RX PubMed=19237752; DOI=10.1107/s0907444908041632;
RA Robbins A.H., Dunn B.M., Agbandje-McKenna M., McKenna R.;
RT "Crystallographic evidence for noncoplanar catalytic aspartic acids in
RT plasmepsin II resides in the Protein Data Bank.";
RL Acta Crystallogr. D 65:294-296(2009).
RN [20] {ECO:0007744|PDB:2R9B}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX PubMed=19271776; DOI=10.1021/bi802059r;
RA Liu P., Marzahn M.R., Robbins A.H., Gutierrez-de-Teran H., Rodriguez D.,
RA McClung S.H., Stevens S.M. Jr., Yowell C.A., Dame J.B., McKenna R.,
RA Dunn B.M.;
RT "Recombinant plasmepsin 1 from the human malaria parasite plasmodium
RT falciparum: enzymatic characterization, active site inhibitor design, and
RT structural analysis.";
RL Biochemistry 48:4086-4099(2009).
RN [21] {ECO:0007744|PDB:4CKU}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX PubMed=24900843; DOI=10.1021/ml4004952;
RA Jaudzems K., Tars K., Maurops G., Ivdra N., Otikovs M., Leitans J.,
RA Kanepe-Lapsa I., Domraceva I., Mutule I., Trapencieris P., Blackman M.J.,
RA Jirgensons A.;
RT "Plasmepsin inhibitory activity and structure-guided optimization of a
RT potent hydroxyethylamine-based antimalarial hit.";
RL ACS Med. Chem. Lett. 5:373-377(2014).
RN [22] {ECO:0007744|PDB:4Y6M, ECO:0007744|PDB:4YA8}
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 125-453 OF WILD TYPE AND OF
RP MUTANT SER-330 IN COMPLEX WITH INHIBITOR, AND DISULFIDE BONDS.
RX PubMed=26625296; DOI=10.1107/s2053230x15022049;
RA Recacha R., Leitans J., Akopjana I., Aprupe L., Trapencieris P.,
RA Jaudzems K., Jirgensons A., Tars K.;
RT "Structures of plasmepsin II from Plasmodium falciparum in complex with two
RT hydroxyethylamine-based inhibitors.";
RL Acta Crystallogr. F 71:1531-1539(2015).
RN [23] {ECO:0007744|PDB:5BWY}
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 78-453, AND DISULFIDE BONDS.
RX PubMed=27599854; DOI=10.1107/s2053230x16011663;
RA Recacha R., Jaudzems K., Akopjana I., Jirgensons A., Tars K.;
RT "Crystal structure of Plasmodium falciparum proplasmepsin IV: the
RT plasticity of proplasmepsins.";
RL Acta Crystallogr. F 72:659-666(2016).
RN [24] {ECO:0007744|PDB:4Z22}
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 125-453 IN COMPLEX WITH
RP INHIBITOR, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX PubMed=26670264; DOI=10.1021/acs.jmedchem.5b01558;
RA Rasina D., Otikovs M., Leitans J., Recacha R., Borysov O.V.,
RA Kanepe-Lapsa I., Domraceva I., Pantelejevs T., Tars K., Blackman M.J.,
RA Jaudzems K., Jirgensons A.;
RT "Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class
RT Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV.";
RL J. Med. Chem. 59:374-387(2016).
CC -!- FUNCTION: During the asexual blood stage, participates in initial
CC cleavage of native host hemoglobin (Hb) resulting in Hb denaturation
CC (PubMed:8844673, PubMed:11782538, PubMed:15574427). May cleave
CC preferentially denatured hemoglobin that has been cleaved by PMI
CC (PubMed:8844673). Digestion of host Hb is an essential step which
CC provides the parasite with amino acids for protein synthesis, and
CC regulates osmolarity (Probable). {ECO:0000269|PubMed:11782538,
CC ECO:0000269|PubMed:15574427, ECO:0000269|PubMed:8844673, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of the bonds linking certain hydrophobic residues
CC in hemoglobin or globin. Also cleaves small molecules substrates such
CC as Ala-Leu-Glu-Arg-Thr-Phe-|-Phe(NO2)-Ser-Phe-Pro-Thr.; EC=3.4.23.39;
CC Evidence={ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:15574427,
CC ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843,
CC ECO:0000269|PubMed:26670264, ECO:0000269|PubMed:8816746,
CC ECO:0000269|PubMed:8844673};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A.
CC {ECO:0000269|PubMed:8844673}.
CC -!- SUBUNIT: Component of the hemozoin formation complex (HFC) composed of
CC falcipain 2, plasmepsins PMII, PMIII/HAP and PMIV, heme detoxifying
CC protein HDP and falcilysin FLN. The HFC complex is involved in
CC hemoglobin degradation and detoxification of heme in the food vacuole
CC during the asexual blood stage. {ECO:0000250|UniProtKB:Q8I6V3}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9169469}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:P39898}. Vacuole
CC lumen {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:9169469}.
CC Vacuole membrane {ECO:0000269|PubMed:9169469}. Note=At the beginning of
CC the asexual blood stage, the transmembrane zymogen is transported to
CC the cytostome, an endocytic structure spanning the parasite cell
CC membrane and the parasitophorous vacuole membrane where host proteins
CC such as hemoglobin are endocytosed (PubMed:9169469). Following
CC endocytosis, localizes to the cytostome vacuole membrane to be then
CC delivered to the digestive (or food) vacuole where it is cleaved into
CC the soluble and active enzyme (PubMed:9169469). In trophozoites,
CC localizes to the digestive vacuole, an acidic vacuole where host
CC hemoglobin is digested (PubMed:9169469, PubMed:11782538).
CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:9169469}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage;
CC expression begins in late rings, increases in trophozoites and
CC continues in schizonts (at protein level).
CC {ECO:0000269|PubMed:11782538, ECO:0000269|PubMed:12850260,
CC ECO:0000269|PubMed:9169469}.
CC -!- PTM: Not N-glycosylated. {ECO:0000269|PubMed:9169469}.
CC -!- PTM: Proteolytically cleaved into the soluble active mature form in the
CC digestive vacuole by cysteine protease falcipains; the process begins
CC at the early ring stage (PubMed:9169469). Proteolysis requires an
CC acidic environment (By similarity). In absence of falcipains,
CC autoprocessing may serve as an alternate activation system (By
CC similarity). {ECO:0000250|UniProtKB:Q8I6V3,
CC ECO:0000269|PubMed:9169469}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; L10740; AAA68217.1; -; Genomic_DNA.
DR EMBL; CH671923; KOB58717.1; -; Genomic_DNA.
DR PDB; 1LEE; X-ray; 1.90 A; A=123-453.
DR PDB; 1LF2; X-ray; 1.80 A; A=123-453.
DR PDB; 1LF3; X-ray; 2.70 A; A=123-453.
DR PDB; 1LF4; X-ray; 1.90 A; A=123-453.
DR PDB; 1M43; X-ray; 2.40 A; A/B=123-453.
DR PDB; 1ME6; X-ray; 2.70 A; A/B=125-453.
DR PDB; 1PFZ; X-ray; 1.85 A; A/B/C/D=77-453.
DR PDB; 1SME; X-ray; 2.70 A; A/B=125-453.
DR PDB; 1W6H; X-ray; 2.24 A; A/B=123-453.
DR PDB; 1W6I; X-ray; 2.70 A; A/C=123-453.
DR PDB; 1XDH; X-ray; 1.70 A; A/B=123-453.
DR PDB; 1XE5; X-ray; 2.40 A; A/B=125-453.
DR PDB; 1XE6; X-ray; 2.80 A; A/B=125-453.
DR PDB; 2BJU; X-ray; 1.56 A; A=1-453.
DR PDB; 2IGX; X-ray; 1.70 A; A=125-453.
DR PDB; 2IGY; X-ray; 2.60 A; A/B=125-453.
DR PDB; 2R9B; X-ray; 2.80 A; A/B=125-453.
DR PDB; 3F9Q; X-ray; 1.90 A; A=125-453.
DR PDB; 4CKU; X-ray; 1.85 A; A/B/C/D/E/F=125-453.
DR PDB; 4Y6M; X-ray; 2.27 A; A/B/C=125-453.
DR PDB; 4YA8; X-ray; 3.30 A; A/B/C/D=125-453.
DR PDB; 4Z22; X-ray; 2.62 A; A/B=125-453.
DR PDB; 5BWY; X-ray; 2.64 A; A=78-453.
DR PDBsum; 1LEE; -.
DR PDBsum; 1LF2; -.
DR PDBsum; 1LF3; -.
DR PDBsum; 1LF4; -.
DR PDBsum; 1M43; -.
DR PDBsum; 1ME6; -.
DR PDBsum; 1PFZ; -.
DR PDBsum; 1SME; -.
DR PDBsum; 1W6H; -.
DR PDBsum; 1W6I; -.
DR PDBsum; 1XDH; -.
DR PDBsum; 1XE5; -.
DR PDBsum; 1XE6; -.
DR PDBsum; 2BJU; -.
DR PDBsum; 2IGX; -.
DR PDBsum; 2IGY; -.
DR PDBsum; 2R9B; -.
DR PDBsum; 3F9Q; -.
DR PDBsum; 4CKU; -.
DR PDBsum; 4Y6M; -.
DR PDBsum; 4YA8; -.
DR PDBsum; 4Z22; -.
DR PDBsum; 5BWY; -.
DR AlphaFoldDB; P46925; -.
DR SMR; P46925; -.
DR BindingDB; P46925; -.
DR ChEMBL; CHEMBL4414; -.
DR DrugBank; DB04378; 3-Amino-N-{4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide.
DR DrugBank; DB04373; 4-Amino-N-{4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB01218; Halofantrine.
DR DrugBank; DB02505; N-(R-Carboxy-Ethyl)-Alpha-(S)-(2-Phenylethyl).
DR DrugBank; DB03063; N-[(2S,3S)-4-[2-[(5S)-3a,4,5,6,7,7a-Hexahydro-1,3-benzodioxol-5-yl]ethyl-[3-(1,3-dioxoisoindol-2-yl)propanoyl]amino]-3-hydroxy-1-phenylbutan-2-yl]-3,5-dimethoxy-4-phenylmethoxybenzamide.
DR MEROPS; A01.023; -.
DR EnsemblProtists; KOB58717; KOB58717; PFHG_00465.
DR VEuPathDB; PlasmoDB:PF3D7_1408000; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000483200; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140013400; -.
DR VEuPathDB; PlasmoDB:PfCD01_140013700; -.
DR VEuPathDB; PlasmoDB:PfDd2_140012600; -.
DR VEuPathDB; PlasmoDB:PfGA01_140013700; -.
DR VEuPathDB; PlasmoDB:PfGB4_140014200; -.
DR VEuPathDB; PlasmoDB:PfGN01_140013300; -.
DR VEuPathDB; PlasmoDB:PfHB3_140013900; -.
DR VEuPathDB; PlasmoDB:PfIT_140014600; -.
DR VEuPathDB; PlasmoDB:PfKE01_140013300; -.
DR VEuPathDB; PlasmoDB:PfKH01_140013600; -.
DR VEuPathDB; PlasmoDB:PfKH02_140013900; -.
DR VEuPathDB; PlasmoDB:PfML01_140013500; -.
DR VEuPathDB; PlasmoDB:PfNF135_140013500; -.
DR VEuPathDB; PlasmoDB:PfNF166_140012200; -.
DR VEuPathDB; PlasmoDB:PfNF54_140013000; -.
DR VEuPathDB; PlasmoDB:PfSD01_140011500; -.
DR VEuPathDB; PlasmoDB:PfSN01_140015400; -.
DR VEuPathDB; PlasmoDB:PfTG01_140013400; -.
DR BioCyc; MetaCyc:MON-15374; -.
DR BRENDA; 3.4.23.39; 4889.
DR EvolutionaryTrace; P46925; -.
DR Proteomes; UP000054289; Unassembled WGS sequence.
DR GO; GO:0031910; C:cytostome; IDA:UniProtKB.
DR GO; GO:0020020; C:food vacuole; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005775; C:vacuolar lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0044002; P:acquisition of nutrients from host; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR034164; Pepsin-like_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Membrane; Protease; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Vacuole; Zymogen.
FT PROPEP 1..124
FT /evidence="ECO:0000269|PubMed:12850260"
FT /id="PRO_0000025930"
FT CHAIN 125..453
FT /note="Plasmepsin II"
FT /id="PRO_0000025931"
FT TOPO_DOM 1..37
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 38..58
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..453
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 140..447
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 338
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT DISULFID 171..176
FT /evidence="ECO:0000269|PubMed:12454457,
FT ECO:0000269|PubMed:12614616, ECO:0000269|PubMed:15840589,
FT ECO:0000269|PubMed:17091526, ECO:0000269|PubMed:19237752,
FT ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843,
FT ECO:0000269|PubMed:26625296, ECO:0000269|PubMed:26670264,
FT ECO:0000269|PubMed:27599854, ECO:0000269|PubMed:8816746,
FT ECO:0000269|PubMed:9886289, ECO:0000269|Ref.11,
FT ECO:0000269|Ref.12, ECO:0000269|Ref.14, ECO:0000269|Ref.15,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:1LEE,
FT ECO:0007744|PDB:1LF2, ECO:0007744|PDB:1LF3,
FT ECO:0007744|PDB:1LF4, ECO:0007744|PDB:1M43,
FT ECO:0007744|PDB:1ME6, ECO:0007744|PDB:1PFZ,
FT ECO:0007744|PDB:1SME, ECO:0007744|PDB:1W6H,
FT ECO:0007744|PDB:1W6I, ECO:0007744|PDB:1XDH,
FT ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6,
FT ECO:0007744|PDB:2BJU, ECO:0007744|PDB:2IGX,
FT ECO:0007744|PDB:2IGY, ECO:0007744|PDB:3F9Q,
FT ECO:0007744|PDB:4CKU, ECO:0007744|PDB:4Y6M,
FT ECO:0007744|PDB:4YA8, ECO:0007744|PDB:4Z22,
FT ECO:0007744|PDB:5BWY"
FT DISULFID 373..409
FT /evidence="ECO:0000269|PubMed:12454457,
FT ECO:0000269|PubMed:12614616, ECO:0000269|PubMed:15840589,
FT ECO:0000269|PubMed:17091526, ECO:0000269|PubMed:19237752,
FT ECO:0000269|PubMed:19271776, ECO:0000269|PubMed:24900843,
FT ECO:0000269|PubMed:26625296, ECO:0000269|PubMed:26670264,
FT ECO:0000269|PubMed:27599854, ECO:0000269|PubMed:8816746,
FT ECO:0000269|PubMed:9886289, ECO:0000269|Ref.11,
FT ECO:0000269|Ref.12, ECO:0000269|Ref.14, ECO:0000269|Ref.15,
FT ECO:0000269|Ref.16, ECO:0007744|PDB:1LEE,
FT ECO:0007744|PDB:1LF2, ECO:0007744|PDB:1LF3,
FT ECO:0007744|PDB:1LF4, ECO:0007744|PDB:1M43,
FT ECO:0007744|PDB:1ME6, ECO:0007744|PDB:1PFZ,
FT ECO:0007744|PDB:1SME, ECO:0007744|PDB:1W6H,
FT ECO:0007744|PDB:1W6I, ECO:0007744|PDB:1XDH,
FT ECO:0007744|PDB:1XE5, ECO:0007744|PDB:1XE6,
FT ECO:0007744|PDB:2BJU, ECO:0007744|PDB:2IGX,
FT ECO:0007744|PDB:2IGY, ECO:0007744|PDB:3F9Q,
FT ECO:0007744|PDB:4CKU, ECO:0007744|PDB:4Y6M,
FT ECO:0007744|PDB:4YA8, ECO:0007744|PDB:4Z22,
FT ECO:0007744|PDB:5BWY"
FT MUTAGEN 241
FT /note="Missing: Reduces catalytic activity towards host
FT hemoglobin."
FT /evidence="ECO:0000269|PubMed:15574427"
FT MUTAGEN 244
FT /note="F->A,K: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:15574427"
FT MUTAGEN 244
FT /note="F->E: Reduces catalytic activity towards host
FT hemoglobin."
FT /evidence="ECO:0000269|PubMed:15574427"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:1PFZ"
FT HELIX 89..99
FT /evidence="ECO:0007829|PDB:1PFZ"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:1PFZ"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:1PFZ"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1PFZ"
FT STRAND 127..135
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 151..158
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 191..200
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 202..217
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 220..231
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 238..241
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1XDH"
FT HELIX 263..269
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 290..296
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 302..313
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 318..325
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 328..337
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 348..354
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 358..362
FT /evidence="ECO:0007829|PDB:1LF2"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1LF2"
FT STRAND 369..372
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 408..411
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:2BJU"
FT HELIX 427..432
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 433..438
FT /evidence="ECO:0007829|PDB:2BJU"
FT TURN 439..442
FT /evidence="ECO:0007829|PDB:2BJU"
FT STRAND 443..449
FT /evidence="ECO:0007829|PDB:2BJU"
SQ SEQUENCE 453 AA; 51490 MW; 0D78A8A65D0C80B5 CRC64;
MDITVREHDF KHGFIKSNST FDGLNIDNSK NKKKIQKGFQ ILYVLLFCSV MCGLFYYVYE
NVWLQRDNEM NEILKNSEHL TIGFKVENAH DRILKTIKTH KLKNYIKESV NFLNSGLTKT
NYLGSSNDNI ELVDFQNIMF YGDAEVGDNQ QPFTFILDTG SANLWVPSVK CTTAGCLTKH
LYDSSKSRTY EKDGTKVEMN YVSGTVSGFF SKDLVTVGNL SLPYKFIEVI DTNGFEPTYT
ASTFDGILGL GWKDLSIGSV DPIVVELKNQ NKIENALFTF YLPVHDKHTG FLTIGGIEER
FYEGPLTYEK LNHDLYWQIT LDAHVGNIML EKANCIVDSG TSAITVPTDF LNKMLQNLDV
IKVPFLPFYV TLCNNSKLPT FEFTSENGKY TLEPEYYLQH IEDVGPGLCM LNIIGLDFPV
PTFILGDPFM RKYFTVFDYD NHSVGIALAK KNL
