4LVO

Crystal structure of PfSUB1-prodomain-NIMP.M7 Fab complex with added CaCl2

Summary for 4LVO

• Entry DOI: 10.2210/pdb4lvo/pdb
• Descriptor: Subtilisin-like serine protease, NIMP.M7 Fab light chain, NIMP.M7 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: alpha beta, enzyme-prodomain complex, rossmann fold, serine protease, calcium ions, prodomain, parasitophorous vacuole, hydrolase-inhibitor-immune system complex, hydrolase/inhibitor/immune system
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 4
• Total formula weight: 95959.34

Authors

Withers-Martinez, C.,Blackman, M.J. (deposition date: 2013-07-26, release date: 2014-05-07, Last modification date: 2023-09-20)

Primary citation

Withers-Martinez, C.,Strath, M.,Hackett, F.,Haire, L.F.,Howell, S.A.,Walker, P.A.,Evangelos, C.,Dodson, G.G.,Blackman, M.J.
The malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin.
Nat Commun, 5:3726-3726, 2014

PubMed Abstract: Malaria is caused by a protozoan parasite that replicates within an intraerythrocytic parasitophorous vacuole. Release (egress) of malaria merozoites from the host erythrocyte is a highly regulated and calcium-dependent event that is critical for disease progression. Minutes before egress, an essential parasite serine protease called SUB1 is discharged into the parasitophorous vacuole, where it proteolytically processes a subset of parasite proteins that play indispensable roles in egress and invasion. Here we report the first crystallographic structure of Plasmodium falciparum SUB1 at 2.25 Å, in complex with its cognate prodomain. The structure highlights the basis of the calcium dependence of SUB1, as well as its unusual requirement for interactions with substrate residues on both prime and non-prime sides of the scissile bond. Importantly, the structure also reveals the presence of a solvent-exposed redox-sensitive disulphide bridge, unique among the subtilisin family, that likely acts as a regulator of protease activity in the parasite.

PubMed: 24785947
DOI: 10.1038/ncomms4726

Experimental method

X-RAY DIFFRACTION (2.26 Å)