7ZNX

Crystal structure of cocaprin 1, inhibitor of cysteine and aspartic proteases from Coprinopsis cinerea

Summary for 7ZNX

• Entry DOI: 10.2210/pdb7znx/pdb
• Descriptor: Cocaprin 1 (2 entities in total)
• Functional Keywords: inhibitor, protein binding
• Biological source: Coprinopsis cinerea
• Total number of polymer chains: 2
• Total formula weight: 30322.82

Authors

Renko, M.,Turk, D.,Sabotic, J. (deposition date: 2022-04-22, release date: 2022-06-01, Last modification date: 2024-01-31)

Primary citation

Renko, M.,Zupan, T.,Plaza, D.F.,Schmieder, S.S.,Perisic Nanut, M.,Kos, J.,Turk, D.,Kunzler, M.,Sabotic, J.
Cocaprins, beta-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.
Int J Mol Sci, 23:-, 2022

PubMed Abstract: We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom , named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.

PubMed: 35563308
DOI: 10.3390/ijms23094916

Experimental method

X-RAY DIFFRACTION (1.6 Å)