5JR6

The Xray Crystal Structure of P. falciparum Aminopeptidase P in Complex With Apstatin

Summary for 5JR6

• Entry DOI: 10.2210/pdb5jr6/pdb
• Related: 5JQK
• Related PRD ID: PRD_000553
• Descriptor: Peptidase, putative, Apstatin, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: aminopeptidase, hydrolase
• Biological source: Plasmodium falciparum (isolate 3D7); More
• Total number of polymer chains: 3
• Total formula weight: 155099.10

Authors

Drinkwater, N.,McGowan, S. (deposition date: 2016-05-05, release date: 2016-08-31, Last modification date: 2023-11-15)

Primary citation

Drinkwater, N.,Sivaraman, K.K.,Bamert, R.S.,Rut, W.,Mohamed, K.,Vinh, N.B.,Scammells, P.J.,Drag, M.,McGowan, S.
Structure and substrate fingerprint of aminopeptidase P from Plasmodium falciparum.
Biochem.J., 473:3189-3204, 2016

PubMed Abstract: 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.

PubMed: 27462122
DOI: 10.1042/BCJ20160550

Experimental method

X-RAY DIFFRACTION (2.3 Å)