Structure and substrate fingerprint of aminopeptidase P from Plasmodium falciparum

Nyssa Drinkwater, Komagal Kannan Sivaraman, Rebecca S. Bamert, Wioletta Rut, Khadija Mohamed, Natalie B. Vinh, Peter J. Scammells, Marcin Drag, Sheena McGowan

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)


Malaria is one of the world's most prevalent parasitic diseases, with over 200 million cases annually. Alarmingly, the spread of drug-resistant parasites threatens the effectiveness of current antimalarials and has made the development of novel therapeutic strategies a global health priority. Malaria parasites have a complicated lifecycle, involving an asymptomatic 'liver stage' and a symptomatic 'blood stage'. During the blood stage, the parasites utilise a proteolytic cascade to digest host hemoglobin, which produces free amino acids absolutely necessary for parasite growth and reproduction. The enzymes required for hemoglobin digestion are therefore attractive therapeutic targets. The final step of the cascade is catalyzed by several metalloaminopeptidases, including aminopeptidase P (APP). We developed a novel platform to examine the substrate fingerprint of APP from Plasmodium falciparum (PfAPP) and to show that it can catalyze the removal of any residue immediately prior to a proline. Further, we have determined the crystal structure of PfAPP and present the first examination of the 3D structure of this essential malarial enzyme. Together, these analyses provide insights into potential mechanisms of inhibition that could be used to develop novel antimalarial therapeutics.

Original languageEnglish
Pages (from-to)3189-3204
Number of pages16
JournalBiochemical Journal
Issue number19
Publication statusPublished - 27 Sep 2016


  • aminopeptidase
  • crystallography
  • malaria
  • plasmodium falciparum
  • protease inhibitor
  • substrate specificity

Cite this