Cucurbit[7]uril‐Dimethyllysine Recognition in a Model Protein

Abstract

Here,weprovide the first structural characterization of host-guest complexation between cucurbit[7]uril (Q7)a nd dimethyllysine (KMe 2 )i nam odel protein. Binding was dominated by complete encapsulation of the dimethylammonium functional group.While selectivity for the most sterically accessible dimethyllysine was observed both in solution and in the solid state,three different modes of Q7-KMe 2 complexation were revealed by X-raycrystallography.The crystal structures revealed also entrapped water molecules that solvated the ammonium group within the Q7 cavity.R emarkable Q7protein assemblies,including inter-locked octahedral cages that comprise 24 protein trimers,o ccurred in the solid state. Cucurbituril clusters appear to be responsible for these assemblies,suggesting astrategy to generate controlled protein architectures.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201803232. Angewandte Chemie Communications Conflict of interestTheauthors declare no conflict of interest.

Atomic Details of Carbon-Based Nanomolecules Interacting with Proteins

“…Cucurbit[7]uril is able to regulate the protein quaternary structure of lectin binding protein. The structure of lectin binding protein in complex with cucurbit[7]uril ( Figure 8 , Table 1 , pdb entry 6f7w) reveals the selective binding of the nanomolecule for post translational modifications of lysine residues, similar to those observed for the structure of sclx 4 , with the side chain of the surface residue hosted within the capsule inner cavity ( Figure 9 ) [ 118 ]. The crystal packing reveals formation of an ordered cucurbiturils cluster that promote assembly of the protein.…”

“…The crystal packing reveals formation of an ordered cucurbiturils cluster that promote assembly of the protein. This study suggests a use of cucurbiturils as a strategy to engineer complex and specific protein architectures [ 118 ]. In summary, the rigid and symmetrical skeleton of cucurbiturils is well suited to interact with phenylalanine and methylated side chain lysine and form clusters to direct protein assembly.…”

Influence of Divalent Cations in the Protein Crystallization Process Assisted by Lanthanide-Based Additives

“…[10][11] However, these solid additives are hardly compatible with the widely-used homogeneous highthroughput crystallisation methods. Recently, new soluble additives were developed that are fully compatible with the automated crystallisation screening systems (Figure 1): i) the polyoxo-metalates developed by Rompel and co-workers, [12][13][14][15] ii) the anionic or neutral macrocycles proposed by the team of Crowley (phosphonated or sulfonato-calix [4,6,8]arenes, and cucurbituryls…), [16][17][18][19] and the lanthanide complexes (iii) tris-dipicolinate [20][21] and iv) crystallophore (Tb-Xo4), 22 developed by our group. All these species can be considered as "molecular glues" inducing a network of supramolecular interactions with proteins in solution, favoring nucleation and crystalline contacts in the packing.…”

Molecular dynamics approach for capturing calixarenes--proteins interactions: the case of cytochrome c

“…The regulation of protein assembly and disassembly mediated by soluble derivatives and based on rational supramolecular approaches has known a growing interest the last decades. 1,2 Indeed, these molecular glues, such as lanthanide coordination complex 3,4 , polyoxometalate clusters 5,6 or organic supramolecular compounds, [7][8][9][10][11] favor protein/additive/protein adduct to create protein material 12 or induce protein crystallization. 13 In that realm, functionalized calixarenes, notably para-sulfonato-calix-[n]-arenes have demonstrated their high potential in biochemistry thanks to their abilities to bind positively charged protein surface to form protein oligomers.…”