Structural profile of ligand-based inhibition of bacterial FtsZ

Abstract

Aim. The idea of the study was to compare and generalize RCSB Protein Data Bank and ChEMBL data in order to establish the structural and biological relationship of experimentaly proved effectors of FtsZ with binding sites. Methods. Literature and database search. Comparison of protein and ligand structures. Protein structure modeling, MD, structural superimposition, etc. Results. The experimental protein-ligand complexes structures of bacterial FtsZ were revised. The structural superimposition of experinental PDB and full-atomic AlphaFold2 models of bacterial FtsZs confirmed their significant structural similarity. Three protein-ligand binding sites were identified by structural alignment. The rating based on database (RCSB Protein Data Bank, ChEMBL, DrugBank, BindingDB, PubChem), patente and literature information on FtsZ-ligand interactions identify perspective sites and main reference compounds. Сonclusions. It was identifyd 3 main protein-ligand binding regions in FtsZ: I. Nucleotide Binding Domain (Ia. Site of GTP/GDP and Ib. MB3 site); II. Site of inter-domain cleft (IDC) and III. Site of coumarin bindig (4HC = 4-hydroxycoumarin). It was indicated that benzamide-binding site, located in the region of inter-domain cleft of FtsZ, demonstrate highest site- and target-specificity.