Backbone resonance assignment of mucoricin: a step towards structural insights into mucor pathogenesis.

Mucoricin is a key virulence factor in mucormycosis, as it targets host endothelial cells and inhibits protein translation through its N-glycosylase activity, leading to vascular leak and increased vascular permeability, thereby contributing to further disease progression. Its structure is quite unique, being structurally homologous to the Ricin B chain as confirmed by cross-reactivity with monoclonal anti-Ricin B chain antibodies, while exhibiting enzymatic activity similar to the Ricin A chain. Here, we report near-complete backbone (Soliman in Nat Microbiol 6(3):313–326, 2021) 1H, 15N, and 13C chemical shift assignments of Mucoricin from Rhizopus delemar at pH 7.5 using NMR spectroscopy. This represents a critical step toward identifying unique structural elements that contribute to its compact structure and toxin activity, which have remained evolutionarily conserved. The secondary structure probabilities derived from the chemical shift data are well aligned with the predicted AlphaFold model, reinforcing the accuracy of the assigned resonances and the structural integrity of recombinant Mucoricin.