5JR6: The Xray Crystal Structure Of P. Falciparum Aminopeptidase P In Complex With Apstatin

Citation:
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.
PDB ID: 5JR6Download
MMDB ID: 142606
PDB Deposition Date: 2016/5/5
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Plasmodium falciparum 3D7
Similar Structures:
Biological Unit for 5JR6: trimeric; determined by author and by software (PISA)
Molecular Components in 5JR6
Label Count Molecule
Proteins (3 molecules)
2
Peptidase, Putative
Molecule annotation
1
Apstatin
Molecule annotation
Chemicals (5 molecules)
1
4
2
1
* Click molecule labels to explore molecular sequence information.

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