BRENDA - Enzyme Database show
show all sequences of 3.4.23.38

Expression and characterization of plasmepsin I from Plasmodium falciparum

Moon, R.P.; Tyas, L.; Certa, U.; Rupp, K.; Bur, D.; Jacquet, C.; Matile, H.; Loetscher, H.; Grueninger-Leitch, F.; et al.; Eur. J. Biochem. 244, 552-560 (1997)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
expression of proplasmepsin I and V110P-proplasmepsin in Escherichia coli; initial attempts to express full-length proplasmepsin I gene in Escherichia coli results in very low expression levels, possibly due to the toxic effects of the hydrophobic segment, and no activation to mature plasmepsin I is ever observed. Recombinant proplasmepsin I is expressed from pETPMI, a construct that is prepared from pET3a and contains the last 48 residues of the propart followed by the 328 residues of mature plasmepsin I. It is necessary to introduce a processing site, V110P, into the zymogen that renders the precursor capable of undergoing autoactivation
Plasmodium falciparum
Engineering
Amino acid exchange
Commentary
Organism
V110P
mutation in proplasmepsin I is responsible for generating a form of proplasmepsin I that is capable of undergoing autoactivation
Plasmodium falciparum
Inhibitors
Inhibitors
Commentary
Organism
Structure
isovaleryl-pepstatin
-
Plasmodium falciparum
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
Plasmodium falciparum
Ro40-4388
-
Plasmodium falciparum
Ro40-5576
-
Plasmodium falciparum
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.01
-
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
0.03
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Plasmodium falciparum
-
-
-
Posttranslational Modification
Posttranslational Modification
Commentary
Organism
proteolytic modification
plasmepsin I is produced as a precursor. The propart region, about 120 residues, is more than twice as long as those of archetypal zymogens
Plasmodium falciparum
Purification (Commentary)
Commentary
Organism
recombinant V110P-proplasmepsin I
Plasmodium falciparum
Source Tissue
Source Tissue
Commentary
Organism
Textmining
additional information
proplasmepsin I is expressed in the ring stages whereas the proplasmepsin II gene is not transcribed until the later trophozoite stage of parasite growth
Plasmodium falciparum
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Ala-Leu-Glu-Arg-Thr-Phe-Leu-Ser-Phe-Pro-Thr + H2O
-
648190
Plasmodium falciparum
Ala-Leu-Glu-Arg-Thr-Phe + Leu-Ser-Phe-Pro-Thr
-
-
-
?
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe + H2O
-
648190
Plasmodium falciparum
Leu-Glu-Arg-Ile-Phe + Phe(NO2)-Ser-Phe
-
-
-
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe + H2O
-
648190
Plasmodium falciparum
Leu-Glu-Arg-Val-Phe + Phe(NO2)-Ser-Phe
-
-
-
-
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
1.3
-
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
1.6
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4
-
hydrolysis of Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
Plasmodium falciparum
pH Range
pH Minimum
pH Maximum
Commentary
Organism
3.5
6
pH 3.5: about 75% of maximal activity, pH 6.0: about 40% of maximal activity, hydrolysis of Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
Plasmodium falciparum
Ki Value [mM]
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
additional information
-
additional information
Ki-value for Ro17-7109 is above 0.05 mM
Plasmodium falciparum
0.000008
-
Ro40-5576
-
Plasmodium falciparum
0.000009
-
Ro40-4388
-
Plasmodium falciparum
0.0003
-
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
Plasmodium falciparum
Cloned(Commentary) (protein specific)
Commentary
Organism
expression of proplasmepsin I and V110P-proplasmepsin in Escherichia coli; initial attempts to express full-length proplasmepsin I gene in Escherichia coli results in very low expression levels, possibly due to the toxic effects of the hydrophobic segment, and no activation to mature plasmepsin I is ever observed. Recombinant proplasmepsin I is expressed from pETPMI, a construct that is prepared from pET3a and contains the last 48 residues of the propart followed by the 328 residues of mature plasmepsin I. It is necessary to introduce a processing site, V110P, into the zymogen that renders the precursor capable of undergoing autoactivation
Plasmodium falciparum
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
V110P
mutation in proplasmepsin I is responsible for generating a form of proplasmepsin I that is capable of undergoing autoactivation
Plasmodium falciparum
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
isovaleryl-pepstatin
-
Plasmodium falciparum
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
Plasmodium falciparum
Ro40-4388
-
Plasmodium falciparum
Ro40-5576
-
Plasmodium falciparum
Ki Value [mM] (protein specific)
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
additional information
-
additional information
Ki-value for Ro17-7109 is above 0.05 mM
Plasmodium falciparum
0.000008
-
Ro40-5576
-
Plasmodium falciparum
0.000009
-
Ro40-4388
-
Plasmodium falciparum
0.0003
-
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
Plasmodium falciparum
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.01
-
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
0.03
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
Posttranslational Modification (protein specific)
Posttranslational Modification
Commentary
Organism
proteolytic modification
plasmepsin I is produced as a precursor. The propart region, about 120 residues, is more than twice as long as those of archetypal zymogens
Plasmodium falciparum
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant V110P-proplasmepsin I
Plasmodium falciparum
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
additional information
proplasmepsin I is expressed in the ring stages whereas the proplasmepsin II gene is not transcribed until the later trophozoite stage of parasite growth
Plasmodium falciparum
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Ala-Leu-Glu-Arg-Thr-Phe-Leu-Ser-Phe-Pro-Thr + H2O
-
648190
Plasmodium falciparum
Ala-Leu-Glu-Arg-Thr-Phe + Leu-Ser-Phe-Pro-Thr
-
-
-
?
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe + H2O
-
648190
Plasmodium falciparum
Leu-Glu-Arg-Ile-Phe + Phe(NO2)-Ser-Phe
-
-
-
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe + H2O
-
648190
Plasmodium falciparum
Leu-Glu-Arg-Val-Phe + Phe(NO2)-Ser-Phe
-
-
-
-
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
1.3
-
Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
1.6
-
Leu-Glu-Arg-Val-Phe-Phe(NO2)-Ser-Phe
pH 4.4, 37°C
Plasmodium falciparum
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4
-
hydrolysis of Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
Plasmodium falciparum
pH Range (protein specific)
pH Minimum
pH Maximum
Commentary
Organism
3.5
6
pH 3.5: about 75% of maximal activity, pH 6.0: about 40% of maximal activity, hydrolysis of Leu-Glu-Arg-Ile-Phe-Phe(NO2)-Ser-Phe
Plasmodium falciparum
Other publictions for EC 3.4.23.38
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
718040
Bhaumik
Crystal structures of the free ...
Plasmodium falciparum
J. Struct. Biol.
175
73-84
2011
-
-
1
1
-
-
1
-
1
-
1
-
-
2
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
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-
1
-
1
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1
-
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1
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1
-
-
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-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
696329
Liu
Recombinant plasmepsin 1 from ...
Plasmodium falciparum
Biochemistry
48
4086-99
2009
-
-
1
-
-
-
8
3
-
-
-
-
-
4
-
1
-
-
-
-
-
-
4
-
-
-
-
3
1
-
-
-
8
-
-
-
-
1
-
-
-
-
-
8
8
3
-
-
-
-
-
-
1
-
-
-
-
-
4
-
-
-
-
3
1
-
-
-
-
-
-
-
-
-
707169
Moura
Role of Plasmodium falciparum ...
Plasmodium falciparum
Antimicrob. Agents Chemother.
53
4968-4978
2009
-
-
-
-
-
-
1
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-
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1
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1
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-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
708121
Friedman
Discovery of plasmepsin inhibi ...
Plasmodium falciparum
ChemMedChem
4
1317-1326
2009
-
-
-
-
-
-
14
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
14
-
-
-
-
-
-
-
14
14
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
680251
Bonilla
Effects on growth, hemoglobin ...
Plasmodium falciparum
Int. J. Parasitol.
37
317-327
2007
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
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-
1
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-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
682004
Bonilla
Critical roles for the digesti ...
Plasmodium falciparum
Mol. Microbiol.
65
64-75
2007
-
-
-
-
-
-
-
-
3
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
682637
Xiao
Expression and enzymatic chara ...
Plasmodium falciparum
Protein Eng. Des. Sel.
20
625-633
2007
-
-
1
-
-
-
1
-
-
-
-
-
-
4
-
1
1
-
-
-
-
-
2
-
-
-
-
-
3
-
-
-
2
-
-
-
-
1
-
-
-
-
-
1
2
-
-
-
-
-
-
-
1
1
-
-
-
-
2
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
667927
Ersmark
Macrocyclic inhibitors of the ...
Plasmodium falciparum
Bioorg. Med. Chem.
14
2197-2208
2006
-
-
-
-
-
-
4
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
-
4
-
-
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4
4
-
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-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
670126
Ersmark
Plasmepsins as potential targe ...
Plasmodium falciparum
Med. Res. Rev.
26
626-666
2006
-
-
-
-
-
-
29
-
-
-
-
-
-
5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
-
29
-
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29
29
-
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-
-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
677552
Hof
Starving the malaria parasite: ...
Plasmodium falciparum
Angew. Chem.
45
2138-2141
2006
-
-
-
-
-
-
4
-
-
-
-
-
-
1
-
-
-
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4
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4
4
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-
679228
Boss
Achiral, cheap, and potent inh ...
Plasmodium falciparum
ChemMedChem
1
1341-1345
2006
-
-
-
-
-
-
13
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
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-
-
-
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-
-
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-
13
-
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13
13
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-
681296
DellAgli
High antiplasmodial activity o ...
Plasmodium falciparum
J. Med. Chem.
49
7440-7449
2006
-
-
-
-
-
-
11
-
-
-
-
-
-
3
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
10
-
10
-
-
-
-
-
-
-
10
11
10
-
-
-
-
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
669779
Johansson
Design and synthesis of potent ...
Plasmodium falciparum
J. Med. Chem.
48
4400-4409
2005
-
-
-
-
-
-
17
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
16
-
-
-
-
-
-
-
-
-
-
17
16
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648181
Ersmark
Potent inhibitors of the Plasm ...
Plasmodium falciparum
J. Med. Chem.
47
110-122
2004
-
-
-
-
-
-
17
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
15
-
-
-
-
-
-
-
-
-
-
17
15
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
669770
Johansson
Design and synthesis of potent ...
Plasmodium falciparum
J. Med. Chem.
47
3353-3366
2004
-
-
-
-
-
-
22
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
21
-
-
-
-
-
-
-
-
-
-
22
21
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648183
Dahlgren
New inhibitors of the malaria ...
Plasmodium falciparum
Bioorg. Med. Chem.
11
3423-3437
2003
-
-
-
-
-
-
12
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
12
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648186
Noteberg
Design and synthesis of plasme ...
Plasmodium falciparum
J. Med. Chem.
46
734-746
2003
-
-
-
-
-
-
12
-
-
-
-
-
-
3
-
-
-
-
-
3
-
-
1
-
-
-
-
-
-
-
-
-
12
-
-
-
-
-
-
-
-
-
-
12
12
-
-
-
-
-
-
-
-
-
-
3
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648187
Siripurkpong
Active Site Contribution to Sp ...
Plasmodium falciparum
J. Biol. Chem.
277
41009-41013
2002
-
-
-
-
-
-
2
1
-
-
-
1
-
1
-
-
1
-
-
-
-
-
2
-
-
-
-
1
-
-
-
-
1
-
1
-
-
-
-
-
-
-
1
2
1
1
-
-
-
1
-
-
-
1
-
-
-
-
2
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
648182
Berry
Plasmepsins as antimalarial ta ...
Plasmodium falciparum
Curr. Opin. Drug Discov. Devel.
3
624-629
2000
-
-
-
-
-
-
3
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
3
2
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
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-
648188
Tyas
Naturally-occurring and recomb ...
Plasmodium falciparum
FEBS Lett.
454
210-214
1999
-
-
-
-
-
-
3
10
-
-
-
-
-
3
-
-
-
-
-
-
-
-
5
-
-
-
-
9
-
-
-
-
5
-
-
-
-
-
-
-
-
-
-
3
5
10
-
-
-
-
-
-
-
-
-
-
-
-
5
-
-
-
-
9
-
-
-
-
-
-
-
-
-
-
648185
Moon
Studies on plasmepsins I and I ...
Plasmodium falciparum
Adv. Exp. Med. Biol.
436
397-406
1998
-
-
-
-
-
-
3
-
-
-
-
-
-
1
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-
-
-
-
-
-
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-
-
-
-
-
-
-
-
-
-
2
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-
-
-
-
-
-
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-
3
2
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-
-
-
-
-
-
-
-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648189
Tyas
Plasmepsins I and II from the ...
Plasmodium falciparum
Adv. Exp. Med. Biol.
436
407-411
1998
-
-
1
-
-
-
3
2
-
-
-
1
-
1
-
-
-
-
-
-
-
-
4
-
-
-
-
2
1
1
-
-
3
-
-
-
-
1
-
-
-
-
-
3
3
2
-
-
-
1
-
-
-
-
-
-
-
-
4
-
-
-
-
2
1
1
-
-
-
-
-
-
-
-
648184
Francis
Biosynthesis and maturation of ...
Plasmodium falciparum
J. Biol. Chem.
272
14961-14968
1997
-
-
-
-
-
-
-
-
2
-
-
1
-
2
-
1
-
-
-
-
-
-
1
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-
-
-
-
-
-
-
-
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-
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-
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-
-
-
2
-
-
1
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648190
Moon
Expression and characterizatio ...
Plasmodium falciparum
Eur. J. Biochem.
244
552-560
1997
-
-
1
-
1
-
4
2
-
-
-
-
-
3
-
1
1
-
-
1
-
-
3
-
-
-
-
2
1
1
-
-
4
-
-
-
-
1
-
-
1
-
-
4
4
2
-
-
-
-
-
-
1
1
-
1
-
-
3
-
-
-
-
2
1
1
-
-
-
-
-
-
-
-
648179
Francis
Molecular characterization and ...
Plasmodium falciparum
EMBO J.
13
306-317
1994
-
-
1
-
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1
-
1
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-
1
-
1
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-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
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-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
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-
-
-
-
648180
Gluzman
Order and specificity of the P ...
Plasmodium falciparum
J. Clin. Invest.
93
1602-1608
1994
-
-
-
-
-
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1
-
1
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1
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-
-
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-
2
-
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-
-
-
-
-
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-
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-
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-
-
-
1
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-
1
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-
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-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
648178
Goldberg
Hemoglobin degradation in the ...
Plasmodium falciparum
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173
961-969
1991
-
-
-
-
-
-
3
-
-
-
1
-
-
1
-
-
1
-
-
-
1
-
1
1
-
-
-
-
1
1
-
-
2
-
1
-
-
-
-
-
-
-
1
3
2
-
-
-
1
-
-
-
-
1
-
-
1
-
1
1
-
-
-
-
1
1
-
-
-
-
-
-
-
-