Summary for peptidase M17.008: M17 aminopeptidase (Plasmodium spp.)

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates Inhibitors

 

Names
MEROPS NameM17 aminopeptidase (Plasmodium spp.)
Other namesaminopeptidase PfLAP, PfA-M17 peptidase
Name and HistoryPfLAP is an aminopeptidase with a strong preference for leucyl bonds (Stack et al., 2007). The native enzyme is a homohexamer, with the active sites directed towards the central cavity. Flexible loops occupy each of the six entrances to the central cavity and regulate access to it. The restricted substrate specificity is governed by a narrow and hyrdophobic primary specificity pocket (McGowan et al., 2010).
Domain architecture
MEROPS Classification
Classification Clan MF >> Subclan (none) >> Family M17 >> Subfamily (none) >> M17.008
HolotypeM17 aminopeptidase (Plasmodium spp.) (Plasmodium falciparum) (peptidase unit: 206-605), MERNUM MER0024892
History Identifier created: MEROPS 7.3 (22 December 2005)
Activity
Catalytic typeMetallo
NC-IUBMBNot yet included in IUBMB recommendations.
pH optimumPfLAP is maximally active at pH 8.5, active over the pH range 7-11 and inactive below pH 6 (Stack et al., 2007).
Inhibitor commentsBestatin and its analogues are potent inhibitors and block parasite growth in culture (Stack et al., 2007).
LocationPfLAP is located in the cytoplasm (Stack et al., 2007).
Biological aspectsPfLAP is produced by all stages of the intra-erythrocytic malarial parasite but especially in the trophozoite (Stack et al., 2007). It has been suggested that because human hemoglobin lacks isoleucine residue, PfLAP helps generate and regulate an internal pool of amino acids, which maintains an osmotically-stable environment and creates a gradient across which rarer amino acids such as isoleucine can pass in exchange for leucine (Stack et al., 2007).
Pharmaceutical relevancePfLAP is a validated drug target and the orally administered chemotherapeutic agent Tosedostat is an inhibitor of both PfLAP and PfA-M1 aminopeptidase. From the tertiary structures of the complexes, the inhibitor binds the substrate binding pockets and the egress channels (Drinkwater et al., 2015).
Distinguishing featuresPfLAP has an N-terminal asparagine-rich region. Recombinant PfLAP lacks this region (McGowan et al., 2010).
Contributing authorsNeil D. Rawlings, InterPro, Proteins Cluster, EMBL European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SD, UK