9HBE | pdb_00009hbe

Making and Breaking Supramolecular Synthons for Modular Protein Frameworks.

(2025) Chemistry : e202500732-e202500732

• PubMed: 40178192 Search on PubMed
• DOI: https://doi.org/10.1002/chem.202500732
• Primary Citation of Related Structures:  
  9HBD, 9HBE, 9HBF, 9HBG


• PubMed Abstract: 
  

  Anionic calixarenes are useful mediators of protein assembly. In some cases, protein - calixarene cocrystallization yields multiple polymorphs. Ralstonia solanacearum lectin (RSL) cocrystallizes with p-sulfonato-calix[8]arene (sclx ₈ ) in at least four distinct pH-dependent arrangements. One of these polymorphs, occurring at pH ≤ 4, is a cubic framework in which RSL nodes are connected by sclx ₈ dimers. These dimers are supramolecular synthons that occur in distinct crystal structures. Now, we show that the discus-shaped dimer of p-phosphonato-calix[6]arene (pclx ₆ ), can replace the sclx ₈ dimer yielding a new assembly of RSL. Remarkably, just one type of RSL - pclx ₆ cocrystal was formed, irrespective of pH or crystallization condition. These results with pclx ₆ contrast starkly with sclx ₈ and suggest that the calixarene type (e.g., phosphonate versus sulfonate) dictates the synthon durability, which in turn exerts control over protein assembly and polymorph selection. Breaking the pclx ₆ dimer required a mutant of RSL with an affinity tag for macrocycle binding. This highly accessible, dicationic site resulted in a significantly altered and porous framework with pclx ₆ (but not with sclx ₈ ). Experiments with ternary mixtures of RSL, pclx ₆ , and sclx ₈ provide evidence of pH-driven self-sorting. Thus, the "mix-and-match" of protein and supramolecular synthons is a promising approach to protein crystal engineering.

   View More

---

Organizational Affiliation: 

School of Biological and Chemical Sciences, University of Galway, University Road, Galway, H91 TK33, Ireland.