Lysins

Lysozyme-like phage lysin
Crystal structure of the modular CPL-1 endolysin from Streptococcus phage Cp-1 complexed with a peptidoglycan analogue. PDB entry 2j8g.
Identifiers
EC number	3.2.1.17
CAS number	9001-63-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Lysins, also known as endolysins or murein hydrolases, are hydrolytic enzymes produced by bacteriophages in order to cleave the host's cell wall during the final stage of the lytic cycle. Lysins are highly evolved enzymes that are able to target one of the five bonds in peptidoglycan (murein), the main component of bacterial cell walls, which allows the release of progeny virions from the lysed cell. These enzymes are being used as antibacterial agents due to their high effectiveness and specificity in comparison with antibiotics, which are susceptible to bacterial resistance.

Not all bacteriophages synthesize lysins, some small single-stranded DNA and RNA phages produce membrane proteins that activate the host's autolytic mechanisms.

Double-stranded DNA phage lysins tend to lie within the 25 to 40 kDa range in terms of size. A notable exception is the streptococcal PlyC endolysin, which is 114 kDa. PlyC is not only the biggest and most potent lysin, but also structurally unique since it is composed of two different gene products, PlyCA and PlyCB, with a ratio of eight PlyCB subunits for each PlyCA in its active conformation.

All other lysins are monomeric and comprise two domains separated by a short linker region. For gram positive bacteria lysins, the N-terminal domain catalyses the hydrolysis of peptidoglycan whereas the C-terminal domain binds to the cell wall substrate.

The catalytic domain is responsible for the cleavage of peptidoglycan bonds. Functionally, five types of lysin catalytic domain can be distinguished:

Peptidoglycan consists of cross-linked amino acids and sugars which form alternating amino sugars: N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Endo-β-N-acetylglucosaminidase lysins cleave NAGs while N-acetylmuramidase lysins (lysozyme-like lysins) cleave NAMs. Endopeptidase lysins cleave any of the peptide bonds between amino acids, whereas N-acetylmuramoyl-l-alanine amidase lysins (or simply amidase lysins) hydrolyze the amide bond between the sugar and the amino acid moieties. Finally, the recently discovered γ-d-glutaminyl-l-lysine endopeptidase lysins cleave the gamma bond between D-glutamine and L-lysine residues.