Accepted_test

Structural studies of the point mutant S25C of the gram-negative targeting endolysin LysSi3 with broad bactericidal activity

by Matyuta I.O. | Sluchanko N.N | Vasina D.V. | Boyko K.M. | Institute of Biochemistry named after A.N. Bach, Research Center of Biotechnology RAS, Moscow, Russia | Institute of Biochemistry named after A.N. Bach, Research Center of Biotechnology RAS, Moscow, Russia | N.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia | Institute of Biochemistry named after A.N. Bach, Research Center of Biotechnology RAS, Moscow, Russia

Abstract ID: 598

Event: BGRS-abstracts

Sections: [Sym 3] Section “Structural biology of proteins nucleic acids and membranes”

Antimicrobial resistance (AMR) is alarmingly increasing in medicine and is one of the major concerns of healthcare today. Due to this fact there is a growing interest in bacteriolytic enzymes that act to lyse bacterial cell wall especially against pathogens with AMR. These types of enzyme include bacteriophage-encoded endolysins which degrade the peptidoglycan (PG) cell wall polymer.

The LysSi3 is a peptidoglycan hydrolyzing, lysozyme-type enzyme with predicted muramidase activity and broad bactericidal activity. LysSi3 was shown to be a monomer in solution. However, a dimer molecule is observed in the structure of the wild type LysSi3. Examination of the dimer interface revealed that the side chains of S25 of the adjacent subunits are in close proximity. To identify the ability of enzyme to form a dimer LysSi3 point mutant S25C (LysSi3^S25C) was obtained and its structure was solved at 1.8 Å resolution using X-ray crystallography. A comparative analysis was carried out with the structure of wild type LysSi3 and it was revealed that the enzyme can form the dimer observed in the structures.