Abstract:Lytic transglycosylases are abundant peptidoglycan lysing enzymes that degrade
the heteropolymers of bacterial cell walls in metabolic processes or in the
course of a bacteriophage infection. The conventional catalytic mechanism of
transglycosylases involves only the Glu or Asp residue. Endolysin gp144 of
Pseudomonas aeruginosa bacteriophage phiKZ belongs to the
family of Gram-negative transglycosylases with a modular composition and
C-terminal location of the catalytic domain. Glu115 of gp144
performs the pre… Show more
“…The catalytic groove of GP144 accommodates five saccharides, as reflected by successful complexation of chitotetraose as a substrate mimic. Interestingly, other evidence suggests that GP144 has two active sites and identifies both E115 and E178 as catalytic residues (Chertkov et al , 2017). GP144 interacts with anionic membranes and causes membrane disruption and eventual lysis, effects not seen in a zwitterionic membrane model (Cloutier et al , 2010).…”
Section: Gram-negative Family 1 Lytic Transglycosylasesmentioning
The lytic transglycosylases (LTs) are bacterial enzymes that catalyze the non-hydrolytic cleavage of the peptidoglycan structures of the bacterial cell wall. They are not catalysts of glycan synthesis as might be surmised from their name. Notwithstanding the seemingly mundane reaction catalyzed by the LTs, their lytic reactions serve bacteria for a series of astonishingly diverse purposes. These purposes include cell-wall synthesis, remodeling, and degradation; for the detection of cell-wall-acting antibiotics; for the expression of the mechanism of cell-wall-acting antibiotics; for the insertion of secretion systems and flagellar assemblies into the cell wall; as a virulence mechanism during infection by certain Gram-negative bacteria; and in the sporulation and germination of Gram-positive spores. Significant advances in the mechanistic understanding of each of these processes have coincided with the successive discovery of new LTs structures. In this review, we provide a systematic perspective on what is known on the structure-function correlations for the LTs, while simultaneously identifying numerous opportunities for the future study of these enigmatic enzymes.
“…The catalytic groove of GP144 accommodates five saccharides, as reflected by successful complexation of chitotetraose as a substrate mimic. Interestingly, other evidence suggests that GP144 has two active sites and identifies both E115 and E178 as catalytic residues (Chertkov et al , 2017). GP144 interacts with anionic membranes and causes membrane disruption and eventual lysis, effects not seen in a zwitterionic membrane model (Cloutier et al , 2010).…”
Section: Gram-negative Family 1 Lytic Transglycosylasesmentioning
The lytic transglycosylases (LTs) are bacterial enzymes that catalyze the non-hydrolytic cleavage of the peptidoglycan structures of the bacterial cell wall. They are not catalysts of glycan synthesis as might be surmised from their name. Notwithstanding the seemingly mundane reaction catalyzed by the LTs, their lytic reactions serve bacteria for a series of astonishingly diverse purposes. These purposes include cell-wall synthesis, remodeling, and degradation; for the detection of cell-wall-acting antibiotics; for the expression of the mechanism of cell-wall-acting antibiotics; for the insertion of secretion systems and flagellar assemblies into the cell wall; as a virulence mechanism during infection by certain Gram-negative bacteria; and in the sporulation and germination of Gram-positive spores. Significant advances in the mechanistic understanding of each of these processes have coincided with the successive discovery of new LTs structures. In this review, we provide a systematic perspective on what is known on the structure-function correlations for the LTs, while simultaneously identifying numerous opportunities for the future study of these enigmatic enzymes.
“…4 b) which suggests that the groove is indeed the active site of the Enc34 endolysin. Furthermore, residues corresponding to Trp79 and Tyr95 are also conserved; these have been shown to be important for catalysis in the structural homologs 27 , 28 , corroborating the evolutionary relatedness of these proteins. Figure 4 Substrate binding groove of the Enc34 endolysin and its structural homologs.…”
Section: Resultsmentioning
confidence: 60%
“…4 b). An equivalent tyrosine residue for Tyr95 and a matching aromatic residue for Trp79 can also be identified in the homologous GH73 and GH23 enzymes where these have been shown to be important for the enzymatic activity, potentially by correctly positioning the substrate in the active site 27 , 28 , 36 . Several other aromatic residues are found in vicinity to the active sites of these enzymes, a not uncommon characteristic for carbohydrate-binding proteins as the aromatic side chains can take part in both hydrogen bonding and non-polar CH-π interactions 37 .…”
Endolysins are bacteriophage-encoded peptidoglycan-degrading enzymes with potential applications for treatment of multidrug-resistant bacterial infections. Hafnia phage Enc34 encodes an unusual endolysin with an N-terminal enzymatically active domain and a C-terminal transmembrane domain. The catalytic domain of the endolysin belongs to the conserved protein family PHA02564 which has no recognizable sequence similarity to other known endolysin types. Turbidity reduction assays indicate that the Enc34 enzyme is active against peptidoglycan from a variety of Gram-negative bacteria including the opportunistic pathogen Pseudomonas aeruginosa PAO1. The crystal structure of the catalytic domain of the Enc34 endolysin shows a distinctive all-helical architecture that distantly resembles the α-lobe of the lysozyme fold. Conserved catalytically important residues suggest a shared evolutionary history between the Enc34 endolysin and GH73 and GH23 family glycoside hydrolases and propose a molecular signature for substrate cleavage for a large group of peptidoglycan-degrading enzymes.
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