Another role of proline: stabilization interactions in proteins and protein complexes concerning proline and tryptophane

Abstract

Proline-tryptophan complexes derived from experimental structures are investigated by quantum chemical procedures known to properly describe the London dispersion energy. We study two geometrical arrangements: the "L-shaped", stabilized by an H-bond, and the "stacked-like", where the two residues are in parallel orientation without any H-bond. Interestingly, the interaction energies in both cases are comparable and very large ( approximately 7 kcal mol(-1)). The strength of stabilization in the stacked arrangement is rather surprising considering the fact that only one partner has an aromatic character. The interaction energy decomposition using the SAPT method further demonstrates the very important role of dispersion energy in such arrangement. To elucidate the structural features responsible for this unexpectedly large stabilization we examined the role of the nitrogen heteroatom and the importance of the cyclicity of the proline residue. We show that the electrostatic interaction due to the presence of the dipole, caused by the nitrogen heteroatom, contributes largely to the strength of the interaction. Nevertheless, the cyclic arrangement of proline, which allows for the largest amount of dispersive contact with the aromatic partner, also has a notable-effect. Geometry optimizations carried out for the "stacked-like" complexes show that the arrangements derived from protein structure are close to their gas phase optimum geometry, suggesting that the environment has only a minor effect on the geometry of the interaction. We conclude that the strength of proline non-covalent interactions, combined with this residue's rigidity, might be the explanation for its prominent role in protein stabilization and recognition processes.

The Structure of HIV-1 Rev Filaments Suggests a Bilateral Model for Rev-RRE Assembly

“…non-globular) sequences (Kay et al, 2000). Further, the C-C interface has a stacking interaction between W45 and P31, a type of interaction which has been shown to be relatively strong despite the absence of any classical hydrogen bonding (Biedermannova et al, 2008). Supporting the importance of this region in forming the C-C interaction, the SV of the interface-participating residues N30 and P31 are the lowest (Fig.…”

Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes

“…Interestingly, all positions occupied by Pro residues in BPP-10c are preserved in BPP10e and BPP-10f sequences (Table V). Therefore, it is important to consider that the restriction of peptide structural solution by Pro residues could be favorable to their biological activities, because Pro could play distinct roles in the structure of peptides/proteins (91). The BK potentiation by BPP-11f was lower than that of BPP-10c and other active peptides (75% Ϯ 6%), although its C-terminal sequence also shows conserved Pro residues.…”

Type II Turn of Receptor-bound Salmon Calcitonin Revealed by X-ray Crystallography

“…6 the CTR ECD, which is potentially a strong interaction. The interaction energy of this kind of proline/tryptophan side chain stacking has been elucidated in a computational study and found to be ϳ7 kcal mol Ϫ1 , despite the fact that only one of the components has an aromatic character (34). It is also illustrated by the decreased binding affinity of [Tyr 32 ]sCT(8 -32) compared with sCT(8 -32) caused by substituting the proline amide residue at position 32 by a tyrosine amide residue.…”