1LF4

STRUCTURE OF PLASMEPSIN II

1LF4 の概要

• エントリーDOI: 10.2210/pdb1lf4/pdb
• 関連するPDBエントリー: 1LEE 1LF2 1LF3 1SME
• 分子名称: Plasmepsin 2 (2 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum)
• 細胞内の位置: Vacuole: P46925
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37123.94

構造登録者

Asojo, O.A.,Gulnik, S.V.,Afonina, E.,Yu, B.,Ellman, J.A.,Haque, T.S.,Silva, A.M. (登録日: 2002-04-10, 公開日: 2002-10-10, 最終更新日: 2024-11-13)

主引用文献

Asojo, O.A.,Gulnik, S.V.,Afonina, E.,Yu, B.,Ellman, J.A.,Haque, T.S.,Silva, A.M.
Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum.
J.Mol.Biol., 327:173-181, 2003

PubMed Abstract: Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-[(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl)-propionyl]-amino]-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5-dimethoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure.

PubMed: 12614616
DOI: 10.1016/S0022-2836(03)00036-6

実験手法

X-RAY DIFFRACTION (1.9 Å)