D-alanine: D-alanine ligase (Ddl), an intracellular bacterial enzyme essential for cell wall biosynthesis, is an attractive target for development of novel antimicrobial drugs. This study focused on an extensive evaluation of two families of Ddl inhibitors encountered in our previous research. New members of both families were obtained through similarity search and synthesis. Ellipticines and 9-acridinylamines were both found to possess inhibitory activity against Ddl from E. coli and antimicrobial activity against E. coli and S. aureus. Ellipticines with a quaternary methylpyridinium moiety were the most potent among all studied compounds, with MIC values as low as 2 mg/L in strains with intact efflux mechanisms. Antimicrobial activity of the studied compounds was connected to membrane damage, making their development as antibacterial drug candidates unlikely unless analogues devoid of this nonspecific effect can be discovered.
COBISS.SI-ID: 4728346
Most biological actions of proteins, including their ability to interact with one another, involve some specific parts of their three-dimensional structure,called binding sites. These have evolved for their ability to bind other molecules effectively and are often conserved in different proteins. Identifying protein-protein binding sites in a protein that is known to interact with other proteins can provide important clues to the function of the protein and can also be used in proteinprotein docking studies to reduce the search space explored by docking algorithms. We have developed an algorithm for structural similarity search in a database of non-redundant protein structures to find conserved binding regions on proteins involved in protein-protein interactions. We have used this algorithm to find conserved regions on a protein surface. The structurally conserved residues found were labeled as a protein-protein binding site, which allowed us to tune the AutoDock docking algorithm to predict the native protein complex structure from unbound protein structures. The conservation of protein structures that correctly predicted protein-protein binding site was used in AutoDock program to improve protein-protein docking. A web application based on our method is available at http://probis.cmm.ki.si.
COBISS.SI-ID: 4787738