Please use this identifier to cite or link to this item: https://scholarhub.balamand.edu.lb/handle/uob/2310
Title: A novel Plasmodium-specific prodomain fold regulates the malaria drug target SUB1 subtilase
Authors: Giganti, David
Bouillon, Anthony
Tawk, Lina 
Robert, Fabienne
Martinez, Mariano
Crublet, Elodie
Weber, Patrick
Girard-Blanc, Christine
Petres, Stéphane
Haouz, Ahmed
Hernandez, Jean-François
Mercereau-Puijalon, Odile
Alzari, Pedro M.
Barale, Jean-Christophe
Affiliations: Department of Medical Laboratory Sciences 
Keywords: Structural biology
Subjects: Molecular biology
Parasitology
Issue Date: 2014
Part of: Journal of nature communications
Issue: 5
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.
URI: https://scholarhub.balamand.edu.lb/handle/uob/2310
Ezproxy URL: Link to full text
Type: Journal Article
Appears in Collections:Department of Medical Laboratory Sciences

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