5MUA

PSL1a-E64 complex

Summary for 5MUA

• Entry DOI: 10.2210/pdb5mua/pdb
• Related: 3PHZ
• Descriptor: Ricin B-related lectin, beta-D-galactopyranose, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: papain-like protease, e-64 inhibitor complex, lectin, calcium-binding, sugar binding protein
• Biological source: Polyporus squamosus
• Total number of polymer chains: 2
• Total formula weight: 63746.65

Authors

Cordara, G.,Manna, D.,Krengel, U. (deposition date: 2017-01-12, release date: 2017-07-12, Last modification date: 2024-01-17)

Primary citation

Cordara, G.,Manna, D.,Krengel, U.
Family of Papain-Like Fungal Chimerolectins with Distinct Ca(2+)-Dependent Activation Mechanism.
Biochemistry, 56:4689-4700, 2017

PubMed Abstract: An important function of fungal lectins is to protect their host. Marasmius oreades agglutinin (MOA) is toxic to nematodes and exerts its protective effect through protease activity. Its proteolytic function is associated with a papain-like dimerization domain. The closest homologue of MOA is Polyporus squamosus lectin 1a (PSL1a). Here, we probed PSL1a for catalytic activity and confirmed that it is a calcium-dependent cysteine protease, like MOA. The X-ray crystal structures of PSL1a (1.5 Å) and MOA (1.3 Å) in complex with calcium and the irreversible cysteine protease inhibitor E-64 elucidated the structural basis for their mechanism of action. The comparison with other calcium-dependent proteases (calpains, LapG) reveals a unique metal-dependent activation mechanism relying on a calcium-induced backbone shift and intradimer cooperation. Intriguingly, the enzymes appear to use a tyrosine-gating mechanism instead of pro-peptide processing. A search for potential MOA orthologues suggests the existence of a whole new family of fungal chimerolectins with these unique features.

PubMed: 28665586
DOI: 10.1021/acs.biochem.7b00317

Experimental method

X-RAY DIFFRACTION (1.49 Å)