7RY7

Structure of Plasmepsin X (PM10, PMX) from Plasmodium falciparum 3D7

「6ORS」から置き換えられました

7RY7 の概要

• エントリーDOI: 10.2210/pdb7ry7/pdb
• 分子名称: Plasmepsin X, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: ssgcid, plasmepsin x, plasmodium falciparum, pm10, pmx, structural genomics, seattle structural genomics center for infectious disease, hydrolase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53364.27

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2021-08-24, 公開日: 2022-02-02, 最終更新日: 2024-10-16)

主引用文献

Kesari, P.,Deshmukh, A.,Pahelkar, N.,Suryawanshi, A.B.,Rathore, I.,Mishra, V.,Dupuis, J.H.,Xiao, H.,Gustchina, A.,Abendroth, J.,Labaied, M.,Yada, R.Y.,Wlodawer, A.,Edwards, T.E.,Lorimer, D.D.,Bhaumik, P.
Structures of plasmepsin X from Plasmodium falciparum reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme.
Protein Sci., 31:882-899, 2022

PubMed Abstract: Plasmodium falciparum plasmepsin X (PfPMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme is involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites.

PubMed: 35048450
DOI: 10.1002/pro.4279

実験手法

X-RAY DIFFRACTION (2.1 Å)