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Crystal structure of MOA in complex with a peptide fragment: A protease caught in flagranti.

ABSTRACT: The Marasmius oreades agglutinin (MOA) is the holotype of an emerging family of fungal chimerolectins and an active Ca²⁺/Mn²⁺-dependent protease, which exhibits a unique papain-like fold with special active site features. Here we investigated the functional significance of the structural elements differentiating MOA from other papain-like cysteine proteases. X-ray crystal structures of MOA co-crystallized with two synthetic substrates reveal cleaved peptides bound to the catalytic site, corresponding to the final products of the proteolytic reaction. Anomalous diffraction data on crystals grown in the presence of calcium and manganese, cadmium or zinc resolve the calcium/manganese preference of MOA and elucidate the inhibitory roles of zinc and cadmium towards papain-like cysteine proteases in general. The reported structures, together with activity data of MOA active site variants, point to a conservation of the general proteolysis mechanism established for papain. Ultimately, the findings suggest that papain and the papain-like domain of MOA are the product of convergent evolution.

SUBMITTER: Manna D

PROVIDER: S-EPMC8244254 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Crystal structure of MOA in complex with a peptide fragment: A protease caught in flagranti.

Manna Dipankar D Cordara Gabriele G Krengel Ute U

Current research in structural biology 20200422

The Marasmius oreades agglutinin (MOA) is the holotype of an emerging family of fungal chimerolectins and an active Ca2+/Mn2+-dependent protease, which exhibits a unique papain-like fold with special active site features. Here we investigated the functional significance of the structural elements differentiating MOA from other papain-like cysteine proteases. X-ray crystal structures of MOA co-crystallized with two synthetic substrates reveal cleaved peptides bound to ...[more]

PMID: 34235469

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Crystal structure of MOA in complex with a peptide fragment: A protease caught in flagranti.

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Crystal structure of MOA in complex with a peptide fragment: A protease caught <i>in flagranti</i>.

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