4TR2

Crystal structure of PvSUB1

4TR2 の概要

• エントリーDOI: 10.2210/pdb4tr2/pdb
• 分子名称: Subtilisin-like 1 serine protease, CALCIUM ION, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: plasmodium egress protease; hydrolase; calcium-binding, hydrolase
• 由来する生物種: Plasmodium vivax
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 147876.28

構造登録者

Giganti, D.,Bouillon, A.,Martinez, M.,Weber, P.,Girard-Blanc, C.,Petres, S.,Haouz, A.,Barale, J.C.,Alzari, P.M. (登録日: 2014-06-13, 公開日: 2014-09-17, 最終更新日: 2024-11-20)

主引用文献

Giganti, D.,Bouillon, A.,Tawk, L.,Robert, F.,Martinez, M.,Crublet, E.,Weber, P.,Girard-Blanc, C.,Petres, S.,Haouz, A.,Hernandez, J.F.,Mercereau-Puijalon, O.,Alzari, P.M.,Barale, J.C.
A novel Plasmodium-specific prodomain fold regulates the malaria drug target SUB1 subtilase.
Nat Commun, 5:4833-4833, 2014

PubMed Abstract: The Plasmodium subtilase SUB1 plays a pivotal role during the egress of malaria parasites from host hepatocytes and erythrocytes. Here we report the crystal structure of full-length SUB1 from the human-infecting parasite Plasmodium vivax, revealing a bacterial-like catalytic domain in complex with a Plasmodium-specific prodomain. The latter displays a novel architecture with an amino-terminal insertion that functions as a 'belt', embracing the catalytic domain to further stabilize the quaternary structure of the pre-protease, and undergoes calcium-dependent autoprocessing during subsequent activation. Although dispensable for recombinant enzymatic activity, the SUB1 'belt' could not be deleted in Plasmodium berghei, suggesting an essential role of this domain for parasite development in vivo. The SUB1 structure not only provides a valuable platform to develop new anti-malarial candidates against this promising drug target, but also defines the Plasmodium-specific 'belt' domain as a key calcium-dependent regulator of SUB1 during parasite egress from host cells.

PubMed: 25204226
DOI: 10.1038/ncomms5833

実験手法

X-RAY DIFFRACTION (2.7 Å)