Bacterial resistance to currently available antibiotic medicines is one of the most serious
public health problems. The inadequate and/or excessive use of antibiotics and the decline
in the development of new antibiotic drugs in recent years contribute to this phenomenon.
For this reason, the development of new antibacterial agents is necessary, and it is useful to
focus this development on the mechanisms necessary for the existence of bacteria, such as
the process of cell division or the biosynthesis of bacterial peptidoglycan. One of the
enzymes that play a key role in the biosynthesis of peptidoglycan is the enzyme UDP-N-acetylmuramate-L-alanine ligase or MurC.
As part of our master's thesis, we attempted to use various bioinformatics tools, databases
and programmes to determine whether the MurC enzyme is a suitable target for the
development of new antibacterial agents. In analysing the enzyme, we focused on key
properties of the potential target, such as gene essentiality, evolutionary conservation of
amino acids and druggability.
We found that the MurC enzyme is essential for 43 bacterial organisms, three of which are
ESKAPE organisms. Using the UniProt online tool, we found that of the bacteria for which
the sequence of the MurC enzyme is known, 11.7% are pathogenic. Using amino acid
evolutionary conservation analysis, queries to predict potential binding sites and queries on
amino acid interactions, we identified 8 amino acid positions best suited for drug targeting.
These amino acid positions of the MurC enzyme are: 128, 129, 130, 131, 173, 326, 346 and
352.
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