7TBB

Crystal structure of Plasmepsin X from Plasmodium falciparum

7TBB の概要

• エントリーDOI: 10.2210/pdb7tbb/pdb
• 分子名称: Plasmepsin 10, 2-acetamido-2-deoxy-beta-D-glucopyranose, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: aspartyl protease, hydrolase
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43734.18

構造登録者

Christensen, J.B.,Hodder, A.N.,Dietrich, M.H.,Scally, S.W.,Cowman, A.F. (登録日: 2021-12-21, 公開日: 2022-05-04, 最終更新日: 2024-10-23)

主引用文献

Hodder, A.N.,Christensen, J.,Scally, S.,Triglia, T.,Ngo, A.,Birkinshaw, R.W.,Bailey, B.,Favuzza, P.,Dietrich, M.H.,Tham, W.H.,Czabotar, P.E.,Lowes, K.,Guo, Z.,Murgolo, N.,Lera Ruiz, M.,McCauley, J.A.,Sleebs, B.E.,Olsen, D.,Cowman, A.F.
Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax.
Structure, 30:947-, 2022

PubMed Abstract: Plasmepsins IX (PMIX) and X (PMX) are essential aspartyl proteases for Plasmodium spp. egress, invasion, and development. WM4 and WM382 inhibit PMIX and PMX in Plasmodium falciparum and P. vivax. WM4 inhibits PMX, while WM382 is a dual inhibitor of PMIX and PMX. To understand their function, we identified protein substrates. Enzyme kinetic and structural analyses identified interactions responsible for drug specificity. PMIX and PMX have similar substrate specificity; however, there are distinct differences for peptide and protein substrates. Differences in WM4 and WM382 binding for PMIX and PMX map to variations in the S' region and engagement of the active site S3 pocket. Structures of PMX reveal interactions and mechanistic detail of drug binding important for development of clinical candidates against these targets.

PubMed: 35460613
DOI: 10.1016/j.str.2022.03.018

実験手法

X-RAY DIFFRACTION (1.85 Å)