1SME

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

1SME の概要

• エントリーDOI: 10.2210/pdb1sme/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000557
• 分子名称: PLASMEPSIN II, Pepstatin (3 entities in total)
• 機能のキーワード: aspartyl proteinase, aspartic proteinase, aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum); 詳細
• 細胞内の位置: Vacuole: P46925
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75279.25

構造登録者

Silva, A.M.,Lee, A.Y.,Gulnik, S.V.,Goldberg, D.E.,Erickson, J.W. (登録日: 1996-06-11, 公開日: 1997-01-11, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)