PROSITE documentation PDOC00737
Glycosyl hydrolases family 25 (GH25) active site signature and domain profile


It has been shown [1,2] that a number of cell-wall lytic enzymes (EC are evolutionary related and can be classified into a single family:

  • Lysozymes (lysin) from Streptococcus pneumoniae bacteriophages of the Cp family.
  • Lysozyme (endolysin) from Lactococcus delbrueckii phage mv1.
  • Autolytic lysozyme from Clostridium acetobutylicum.
  • Lysozyme M1 from Streptomyces globisporus.
  • N,O-diacetylmuramidase (lysozyme ch) from the fungus Chalaropsis.

These proteins belong to the Chalaropsis (Ch)-type lyzozymes or glycosyl hydrolases family 25 (GH25) [E1]. The Ch-type lysozymes family GH25 exhibits both β-1,4-N-acetylmuramidase and β-1,4-N,6-O-diacetylmuramidase activities and its evolutionary spread is diverse, comprising bacterial, viral (mainly phage) and eukaryotic representatives.

The Ch-type lysozyme domain is structurally unrelated to the other lysozyme folds. It has a β/α-barrel fold and is composed of eight β-strands and six α-helices, with the strands forming the staves of the barrel and the helices located around it (see <PDB:1JFX>). A conserved active-site DxE motif may be implicated in catalysis, which could proceed through an oxazoline intermediate. The aspartate residue has been proposed to be the catalytic acid/base, initially protonating the leaving group to facilitate its departure (general acid assistance) and subsequently acting as a general base to activate the hydrolytic water molecule. The glutamate residue acts to stabilize or deprotonate the oxazoline N atom [3,4]. A third residue, Asp6 of the profile, could also be involved in catalysis with the Glu of the DxE motif if the hydrolysis occurs via a net inversion of the anomeric configuration, with Asp6 acting as the general base, helping to activate the nucleophilic water molecule, and the Glu of the DxE motif acting as the general acid, protonating the departing oxygen atom in a concerted fashion as the bond cleaves [5,6].

Two residues, an aspartate and a glutamate, as well as some others in their vicinity are conserved in all proteins from this family and can be used as a signature pattern. We also developed a profile which covers the entire Ch-type lysozyme domain.

Expert(s) to contact by email:

Henrissat B.

Last update:

August 2019 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

GLYCOSYL_HYDROL_F25_2, PS51904; Glycosyl hydrolase family 25 (GH25) domain profile  (MATRIX)

GLYCOSYL_HYDROL_F25_1, PS00953; Glycosyl hydrolases family 25 active site signature  (PATTERN)


1AuthorsCroux C. Garcia J.L.
TitleSequence of the lyc gene encoding the autolytic lysozyme of Clostridium acetobutylicum ATCC824: comparison with other lytic enzymes.
SourceGene 104:25-31(1991).
PubMed ID1916274

2AuthorsHenrissat B.
TitleA classification of glycosyl hydrolases based on amino acid sequence similarities.
SourceBiochem. J. 280:309-316(1991).
PubMed ID1747104

3AuthorsRau A. Hogg T. Marquardt R. Hilgenfeld R.
TitleA new lysozyme fold. Crystal structure of the muramidase from Streptomyces coelicolor at 1.65 A resolution.
SourceJ. Biol. Chem. 276:31994-31999(2001).
PubMed ID11427528

4AuthorsKorczynska J.E. Danielsen S. Schagerloef U. Turkenburg J.P. Davies G.J. Wilson K.S. Taylor E.J.
TitleThe structure of a family GH25 lysozyme from Aspergillus fumigatus.
SourceActa Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 66:973-977(2010).
PubMed ID20823508

5AuthorsHermoso J.A. Monterroso B. Albert A. Galan B. Ahrazem O. Garcia P. Martinez-Ripoll M. Garcia J.L. Menendez M.
TitleStructural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1.
SourceStructure 11:1239-1249(2003).
PubMed ID14527392

6AuthorsAl-Riyami B. Uestok F.I. Stott K. Chirgadze D.Y. Christie G.
TitleThe crystal structure of Clostridium perfringens SleM, a muramidase involved in cortical hydrolysis during spore germination.
SourceProteins 84:1681-1689(2016).
PubMed ID27488615


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