Structural and functional characterization of Group B Streptococcus class C sortases

In Group B Streptococcus (GBS) three structurally distinct types of pili have been discovered as potential virulence factors and vaccine candidates. The pilus-forming proteins are assembled into high-molecular weight polymers via a transpeptidation mechanism mediated by specific class C sortases. Using a multidisciplinary approach including bioinformatics, structural and biochemical studies and in vivo mutagenesis we performed a broad characterization of GBS sortase C. The high resolution X-ray structure of the enzymes revealed that the active site, located into the β-barrel core of the enzyme, is made of the catalytic triad His157-Cys219-Arg228 and covered by a loop, known as the “lid”. We show that the catalytic triad and the predicted N- and C-terminal trans-membrane regions are required for the enzyme activity. Interestingly, by in vivo complementation mutagenesis studies we found that the deletion of the entire lid loop or mutations in specific lid key residues had no effect on catalytic activity of the enzyme. In addition, kinetic characterizations of recombinant enzymes indicate that the lid mutants can still recognize and cleave the substrate-mimicking peptide at least as well as the wild type protein.

The conceptualisation of music in ancient Greek thought (V century B.C. – II century B.C.)

The focus of this dissertation is the analysis of the music-related philosophical passages from the 5th century B.C. to the 2nd century B.C. It aims to provide a multifaceted view towards music as a cultural phenomenon, which is based primarily on the philological and culturological explorations instead of the technical-musicological approach. The texts from our selected period attest that mousikē had an extremely broad conceptualisation which led to the attribution of the different, sometimes completely opposite value: from an insignificant performative practice to an activity which corresponds to the divine laws and directly affects the human soul. The discussed testimonia provide evidence of defining music both as an exclusively acoustic phenomenon and as a philosophically significant concept that oversteps the sonic definition. Our sources clearly demonstrate that mousikē was a polysemous term: it was understood as an interdisciplinary form of art (as the arts of the Muses), though it was also used to indicate the exclusively instrumental music or a philosophical concept, which does not necessarily define sound as its essential quality. The aim of this dissertation is to clarify the arguments behind each of these positions, to analyse whether such different modes of conceptualisation are compatible among themselves, and to see how they fit together into explaining what was understood as music in Antiquity. In this thesis we explore the conceptual framework of mousikē and analyse what enabled the musical thought to be worthy of the attention of the greatest philosophical minds. We will demonstrate that it was not the sound or the artistic practices that were central in the philosophical thought on music, but instead the embedded structural qualities that have correspondence to the universal proportions of the cosmic world and which are perceptible to the listeners through the medium of sound.