Summary for peptidase A01.075: plasmepsin-5 (Plasmodium sp.)

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates Inhibitors

 

Names
MEROPS Nameplasmepsin-5 (Plasmodium sp.)
Other namesplasmepsin V
Name and HistoryThe malaria parasite has to remodel its host erythrocyte and to do this a few hundred proteins are exported into the host cell. A protein destined for export contains a PEXEL (Plasmodium Export Element) motif (Arg-Xaa-Leu-Xaa-(Glu/Gln/Asp) downstream of the signal peptide. This targets the protein to the endoplasmic reticulum. Plasmepsin-5 removes the PEXEL motif (Russo et al., 2010).
Domain architecture
MEROPS Classification
Classification Clan AA >> Subclan (none) >> Family A1 >> Subfamily B >> A01.075
Holotypeplasmepsin-5 (Plasmodium sp.) (Plasmodium falciparum) (peptidase unit: 77-442), MERNUM MER0031143
History Identifier created: MEROPS 7.5 (14 July 2006)
Activity
Catalytic typeAspartic
NC-IUBMBNot yet included in IUBMB recommendations.
SpecificityCleavage occurs at the leucyl bond in the PEXEL motif and the residues that accommodate Arg in P3 have been identified by modelling of structures (Guruprasad et al., 2011). Several exported proteins lacking the canonical PEXEL motif are also processed, but proteins with Lys at P3 or Ile at P1 are not processed by plasmepsin-5 (Boddey et al., 2013).
pH optimumPlasmepsin-5 is active in the pH range 5-7 with optimal activity at pH 6.5 (Russo et al., 2010).
Special substrateDABCYL-LNKRLLHETQ-E(EDANS) (Xiao et al., 2014).
Special inhibitorWEHI-842 (Hodder et al., 2015).
Inhibitor commentsPlasmepsin-5 does not bind pepstatin-Sepharose (Klemba et al., 2005) and is only weakly inhibited by pepstatin (Xiao et al., 2014).
StructurePlasmepsin-5 is a type I integral membrane protein, with a long C-terminal transmembrane region and a cytoplasmic tail (Klemba et al., 2005).
LocationPlasmepsin-5 is a membrane-associated protein with the peptidase domain in the lumen of the endoplasmic reticulum (Russo et al., 2010). The gene is expressed in all intra-erythrocytic stages (Klemba et al., 2005).
PhysiologyPlasmepsin-5 removes the PEXEL targeting motif from proteins destined for export to the host cell (Russo et al., 2010).
Biological aspectsPlasmepsin-5 is synthesized as a precursor, but surprisingly the precursor is enzymically active (Xiao et al., 2014).
Contributing authorsNeil D. Rawlings, InterPro, Proteins Cluster, EMBL European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SD, UK
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Plasmepsin