Structural and mechanistic investigations on Salmonella typhimurium acetate kinase (AckA): identification of a putative ligand binding pocket at the dimeric interface

Background

A large number of studies have been carried out to obtain amino acid propensities for ??-helices and ??-sheets. The obtained propensities for ??-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the ??-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects ??-sheet propensity.

Results

We calculated amino acid propensities for ??-helices and ??-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that ??-helix propensities do not differ significantly by fold, but ??-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for ??-helix, but such is not the case for the ??-sheet propensities. We also found some fold dependence on amino acid frequency in ??-strands. Folds with a high Ser, Thr and Asn content at exposed sites in ??-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = ?0.90) and to have flat ??-sheets. At buried sites in ??-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = ?0.93). "All-??" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "??/??" proteins tend to have a higher content of Val, Ile and Leu.

Conclusions

The ??-helix propensities are similar for all folds and for exposed and buried residues. However, ??-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in ??-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding properties such as the twist of a ??-strand or association between two ?? sheets.