부산대학교 도서관

To achieve productive binding, enzymes and substrates must align their geometries to complement each other along an entire substrate binding site, which may require enzyme flexibility. In pursuit of novel drug targets for the human pathogen S. aureus, we studied peptidoglycan N-acetylglucosaminidases, whose structures are composed of two domains forming a V-shaped active site cleft. Combined insights from crystal structures supported by site-directed mutagenesis, modeling, and molecular dynamics enabled us to elucidate the substrate binding mechanism of SagB and AtlA-gl. This mechanism requires domain sliding from the open form observed in their crystal structures, leading to polysaccharide substrate binding in the closed form, which can enzymatically process the bound substrate. We suggest that these two hydrolases must exhibit unusual extents of flexibility to cleave the rigid structure of a bacterial cell wall. Pintar et al. identify a substrate-binding mechanism of bacterial peptidoglycan N-acetylglucosaminidases. They find that a domain sliding from an open form of these enzymes, which can bind substrates, to their closed form triggers substrate catalysis. This study highlights the structural flexibility of enzymes, which accommodates the structure to process their substrates. [ABSTRACT FROM AUTHOR]