1QS8

Crystal structure of the P. vivax aspartic proteinase plasmepsin complexed with the inhibitor pepstatin A

1QS8 の概要

• エントリーDOI: 10.2210/pdb1qs8/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000557
• 分子名称: PLASMEPSIN, PEPSTATIN A, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: plasmepsin, aspartic proteinase, haemoglobinase, malaria, pepstatin a, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Plasmodium vivax (malaria parasite P. vivax); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75807.57

構造登録者

Khazanovich Bernstein, N.,Cherney, M.M.,Yowell, C.A.,Dame, J.B.,James, M.N.G. (登録日: 1999-06-25, 公開日: 1999-07-07, 最終更新日: 2024-11-06)

主引用文献

Bernstein, N.K.,Cherney, M.M.,Yowell, C.A.,Dame, J.B.,James, M.N.
Structural insights into the activation of P. vivax plasmepsin.
J.Mol.Biol., 329:505-524, 2003

PubMed Abstract: The malarial aspartic proteinases (plasmepsins) have been discovered in several species of Plasmodium, including all four of the human malarial pathogens. In P.falciparum, plasmepsins I, II, IV and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets for anti-malarial drug design. The plasmepsins are produced from inactive zymogens, proplasmepsins, having unusually long N-terminal prosegments of more than 120 amino acids. Structural and biochemical evidence suggests that the conversion process of proplasmepsins to plasmepsins differs substantially from the gastric and plant aspartic proteinases. Instead of blocking substrate access to a pre-formed active site, the prosegment enforces a conformation in which proplasmepsin cannot form a functional active site. We have determined crystal structures of plasmepsin and proplasmepsin from P.vivax. The three-dimensional structure of P.vivax plasmepsin is typical of the monomeric aspartic proteinases, and the structure of P.vivax proplasmepsin is similar to that of P.falciparum proplasmepsin II. A dramatic refolding of the mature N terminus and a large (18 degrees ) reorientation of the N-domain between P.vivax proplasmepsin and plasmepsin results in a severe distortion of the active site region of the zymogen relative to that of the mature enzyme. The present structures confirm that the mode of inactivation observed originally in P.falciparum proplasmepsin II, i.e. an incompletely formed active site, is a true structural feature and likely represents the general mode of inactivation of the related proplasmepsins.

PubMed: 12767832
DOI: 10.1016/S0022-2836(03)00444-3

実験手法

X-RAY DIFFRACTION (2.5 Å)