Computational insights into the circular permutation roles on ConA binding and structural stability

The mechanisms behind Concanavalin A (ConA) circular permutation have been under investigation since 1985. Although a vast amount is known about this lectin and its uses, the exact purpose of its processing remains unclear. To shed light on this, this study employed computer simulations to compare the unprocessed ProConA with the mature ConA. This approach aimed to reveal the importance of the post-translational modification, especially how they affect the lectin stability and carbohydrate-binding properties. To achieve these goals, we conducted 200 ns molecular dynamics simulations and trajectory analyses on the monomeric forms of ProConA and ConA (both unbound and in complex with D-mannose and the GlcNAc2Man9 N-glycan), as well as on their oligomeric forms. Our findings reveal significant stability differences between ProConA and ConA at both the monomeric and tetrameric levels, with ProConA exhibiting consistently lower stability parameters compared to ConA. In terms of carbohydrate binding, however, both lectins showed remarkable similarities in their interaction profiles, contact numbers, and binding free energies with D-mannose and the N-glycan. Overall, our results suggest that the processing of ProConA significantly enhances the mature lectin stability, especially in maintaining the tetrameric oligomer, without substantially affecting its carbohydrate-binding properties.