Abstract
Endolysins are peptidoglycan-degrading enzymes utilized by bacteriophages to release the progeny from bacterial cells. The lytic properties of phage endolysins make them potential antibacterial agents for medical and industrial applications. Here, we present a comprehensive characterization of phage AP3 modular endolysin (AP3gp15) containing cell wall binding domain and an enzymatic domain (DUF3380 by BLASTP), both widespread and conservative. Our structural analysis demonstrates the low similarity of an enzymatic domain to known lysozymes and an unusual catalytic centre characterized by only a single glutamic acid residue and no aspartic acid. Thus, our findings suggest distinguishing a novel class of muralytic enzymes having the activity and catalytic centre organization of DUF3380. The lack of amino acid sequence homology between AP3gp15 and other known muralytic enzymes may reflect the evolutionary convergence of analogous glycosidases. Moreover, the broad antibacterial spectrum, lack of cytotoxic effect on human cells and the stability characteristics of AP3 endolysin advocate for its future application development.
Highlights
Endolysins are peptidoglycan-degrading enzymes utilized by bacteriophages to release the progeny from bacterial cells
Muralytic enzymes are peptidoglycan (PG) degrading proteins widely represented within bacteriophages, bacteria, archaea, and eukaryotes
Muralytic enzymes may occur as virion-associated lysins serving for PG degradation at the first step of host infection, or as endolysins required at the end of a viral lytic cycle to allow progeny release from the infected cell[1,2,3]
Summary
Endolysins are peptidoglycan-degrading enzymes utilized by bacteriophages to release the progeny from bacterial cells. AP3 modular endolysin (AP3gp15) containing cell wall binding domain and an enzymatic domain (DUF3380 by BLASTP), both widespread and conservative. Muralytic enzymes may occur as virion-associated lysins serving for PG degradation at the first step of host infection, or as endolysins required at the end of a viral lytic cycle to allow progeny release from the infected cell[1,2,3]. Endolysins have a limited activity against Gram-negatives because of their impermeable outer membrane (OM) which protects the bacterial cell wall from exogenous. The vast majority of known endolysins derived from Gram-negatives infecting phages are 15–20 kDa proteins containing a single enzymatic domain of simple globular structure.
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