4TR2

Crystal structure of PvSUB1

Summary for 4TR2

• Entry DOI: 10.2210/pdb4tr2/pdb
• Descriptor: Subtilisin-like 1 serine protease, CALCIUM ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: plasmodium egress protease; hydrolase; calcium-binding, hydrolase
• Biological source: Plasmodium vivax
• Total number of polymer chains: 2
• Total formula weight: 147876.28

Authors

Giganti, D.,Bouillon, A.,Martinez, M.,Weber, P.,Girard-Blanc, C.,Petres, S.,Haouz, A.,Barale, J.C.,Alzari, P.M. (deposition date: 2014-06-13, release date: 2014-09-17, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)