Abstract

Fungal pathways of essential amino acids biosynthesis provide an abundant source of molecular targets for new antifungal compounds, among which the L-methionine biosynthesis pathway (MBP) may be promising. In this dissertation I characterized three C. albicans enzymes involved in MBP: homoserine O-acetyltransferase (CaMet2p), O-acetyl-L-homoserine sulfhydrylase (CaMet15p), and cystathionine-γ-synthase (CaStr2p). I performed crystallization trials of analyzed proteins, which led to the formation of a CaMet15p crystal of 7 Å resolution. Additionally, I proved that the inhibition of CaMet2p, CaMet15p, and CaStr2p induces fungal growth deficiency dependent on L-methionine (L-Met) presence. Among variety of examined potential inhibitors, I selected L-penicillamine (L-PEN) as the most effective against CaMet2p enzyme, and β-(5-Oxo-3-isoxazolin-2-yl)-L-alanine as an inhibitor of CaMet15p and CaStr2p. Moreover, I have assessed antifungal effect induced by combination of inhibitors, which showed a synergistic effect b

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