1SME

PLASMEPSIN II, A HEMOGLOBIN-DEGRADING ENZYME FROM PLASMODIUM FALCIPARUM, IN COMPLEX WITH PEPSTATIN A

Summary for 1SME

• Entry DOI: 10.2210/pdb1sme/pdb
• Related PRD ID: PRD_000557
• Descriptor: PLASMEPSIN II, Pepstatin (3 entities in total)
• Functional Keywords: aspartyl proteinase, aspartic proteinase, aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Plasmodium falciparum (malaria parasite P. falciparum); More
• Cellular location: Vacuole: P46925
• Total number of polymer chains: 4
• Total formula weight: 75279.25

Authors

Silva, A.M.,Lee, A.Y.,Gulnik, S.V.,Goldberg, D.E.,Erickson, J.W. (deposition date: 1996-06-11, release date: 1997-01-11, Last modification date: 2024-10-23)

Primary citation

Silva, A.M.,Lee, A.Y.,Gulnik, S.V.,Maier, P.,Collins, J.,Bhat, T.N.,Collins, P.J.,Cachau, R.E.,Luker, K.E.,Gluzman, I.Y.,Francis, S.E.,Oksman, A.,Goldberg, D.E.,Erickson, J.W.
Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.
Proc.Natl.Acad.Sci.USA, 93:10034-10039, 1996

PubMed Abstract: Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture.

PubMed: 8816746
DOI: 10.1073/pnas.93.19.10034

Experimental method

X-RAY DIFFRACTION (2.7 Å)