Structural Characterization of Lytic Transglycosylase SltB2 of Pseudomonas aeruginosa

TL;DR

This paper reveals the crystal structure of SltB2, a cell-wall enzyme in Pseudomonas aeruginosa, and explains how it interacts with peptidoglycan.

Contribution

The study provides a high-resolution crystal structure of SltB2 and proposes a model for its interaction with peptidoglycan.

Findings

SltB2 has a unique modular architecture with a peptidoglycan-binding domain.

The enzyme's exolytic activity is explained by structural features at site +2.

Comparative analysis reveals insights into substrate recognition and function in family 3 lytic transglycosylases.

Abstract

Lytic transglycosylases (LTs) belong to a family of enzymes
that
turnover the bacterial cell-wall peptidoglycan through a nonhydrolytic
cleavage of the β(1–4) glycosidic bond, generating a
hallmark 1,6-anhydromuramyl moiety in the reaction products. LTs are
essential for numerous cellular processes, including cell-wall maturation,
peptidoglycan recycling, cell division, and the assembly of multiprotein
complexes. Their functional diversity underscores their biological
significance. Family 3 LTs are distinguished by their EF-hand Ca2+-binding motif and are classified into two subfamilies. Subfamily
3B members, including Pseudomonas aeruginosa SltB2, possess a peptidoglycan-binding domain absent in subfamily
3A. In this study, we present the structural characterization of P. aeruginosa SltB2. The high-resolution crystal
structure of SltB2 reveals a unique modular architecture shaped by
the specific arrangement of its PG-binding domain and distinct differences
in the organization of key residues surrounding the catalytic Glu
residue compared to other family 3 members. A model of interaction
between SltB2 and the peptidoglycan is proposed, which accounts for
the enzyme’s tolerance to peptide stems and reveals particular
features at site +2, due to the unique arrangement of the PG-binding
domain, explaining its preferred exolytic activity. Comparative structural
analyses of Family 3 LTs provide insights into substrate recognition
and enzymatic function, advancing our understanding of bacterial cell-wall
remodeling mechanisms.

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