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Literature summary for 3.4.23.B14 extracted from
- Activity and inhibition of plasmepsin IV, a new aspartic proteinase from the malaria parasite, Plasmodium falciparum (2002), FEBS Lett., 513, 159-162.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | plasmepsin IV appears to be a potential target for the development of new antiparasitic drugs. Plasmepsin I, II and IV might act in concert. While this might suggest that inhibition of individual enzymes might be insufficient to kill the parasite, the broad similarities between the plasmepsins may permit the development of compunds able to inhibit all three enzymes to produce a drug capable of imposing a multiple blockade on the pathway of haemoglobin digestion | Plasmodium falciparum |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression in Escherichia coli | Plasmodium falciparum |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-Val-Val-Sta-Ala-Sta | - |
Plasmodium falciparum |  |
| isobutyl-Val-Val-Sta-Ala-Sta | - |
Plasmodium falciparum | |
| Iva-Val-Val-Sta-Ala-Sta | - |
Plasmodium falciparum | |
| Lac-Val-Sta-Ala-Sta | - |
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 | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.011 | - |
KEFVFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
| 0.02 | - |
KEFNFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
| 0.035 | - |
KEFAFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
| 0.036 | - |
KPIEFZRL | pH 4.7, 37°C | Plasmodium falciparum | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| vacuole | digestive vacuole | Plasmodium falciparum | 5773 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| haemoglobin + H2O | Plasmodium falciparum | human haemoglobin. The enzyme may play a crucial role in the critical process which yields nutrients from parasite growth, the enzyme may have the potential to initiate the vacuolar haemoglobin digestion pathway | ? | - |
? | |
| additional information | Plasmodium falciparum | since plasmepsin IV clearly can cleave within the -Ser-(Phe/Leu)-Lys-Phe-Phe-Lys-(Ser/Thr)-Gly- sequence it may be possible that plasmepsin IV initiates cleavage of the proplasmepsin I precursor | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Plasmodium falciparum | Q8IM16 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | incubation of the 44000 Da proplasmepsin IV at pH 4.7 results in its conversion to a protein of 38000 Da. Autoactivation site in proplasmepsin IV -KESFKF-/-F-/-KSGYAQ- | Plasmodium falciparum |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| haemoglobin + H2O | human haemoglobin. At pH 4.7, the enzyme is able to degrade hemoglobin so that no bands remain visible on SDS-PAGE. When excess of hemoglobin is used a 14000 Da band is detected, consistent with a cleavage of the alpha-globin chain at the Phe33-Leu34 bond in the hinge region of the molecule | Plasmodium falciparum | ? | - |
? | |
| haemoglobin + H2O | human haemoglobin. The enzyme may play a crucial role in the critical process which yields nutrients from parasite growth, the enzyme may have the potential to initiate the vacuolar haemoglobin digestion pathway | Plasmodium falciparum | ? | - |
? | |
| KEFAFF(NO2)ALK + H2O | - |
Plasmodium falciparum | KEFAF + F(NO2)ALK | - |
? | |
| KEFNFF(NO2)ALK + H2O | - |
Plasmodium falciparum | KEFNF + F(NO2)ALK | - |
? | |
| KEFVFF(NO2)ALK + H2O | - |
Plasmodium falciparum | KEFVF + F(NO2)ALK | - |
? | |
| KPIEFZRL + H2O | - |
Plasmodium falciparum | KPIEF + ZRL | - |
? | |
| additional information | since plasmepsin IV clearly can cleave within the -Ser-(Phe/Leu)-Lys-Phe-Phe-Lys-(Ser/Thr)-Gly- sequence it may be possible that plasmepsin IV initiates cleavage of the proplasmepsin I precursor | Plasmodium falciparum | ? | - |
? | |
| spectrin + H2O | - |
Plasmodium falciparum | ? | - |
? | |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 5 | - |
KPIEFZRL | pH 4.7, 37°C | Plasmodium falciparum | |
| 6 | - |
KEFVFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
| 13 | - |
KEFAFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
| 20 | - |
KEFNFF(NO2)ALK | pH 4.7, 37°C | Plasmodium falciparum | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | the Ki-value for isobutyl-Val-Val-Sta-Ala-Sta is below 0.1 nM | Plasmodium falciparum | |
| 0.0000001 | - |
Iva-Val-Va-Sta-Ala-Sta | pH 4.7 | Plasmodium falciparum | |
| 0.0000002 | - |
acetyl-Val-Val-Sta-Ala-Sta | pH 4.7 | Plasmodium falciparum | |
| 0.00001 | - |
Ro40-4388 | pH 4.7 | Plasmodium falciparum | |
| 0.000015 | - |
Ro40-5576 | pH 4.7 | Plasmodium falciparum | |
| 0.000025 | - |
Lac-Val-Sta-Ala-Sta | pH 4.7 | Plasmodium falciparum | |
| 0.00005 | - |
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide | pH 4.7 | Plasmodium falciparum | |
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