Structure and Cell Wall Cleavage by Modular Lytic Transglycosylase MltC of Escherichia coli

The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative b...

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Bibliographic Details
Published in:ACS chemical biology 2014-09, Vol.9 (9), p.2058-2066
Main Authors: Artola-Recolons, Cecilia, Lee, Mijoon, Bernardo-García, Noelia, Blázquez, Blas, Hesek, Dusan, Bartual, Sergio G, Mahasenan, Kiran V, Lastochkin, Elena, Pi, Hualiang, Boggess, Bill, Meindl, Kathrin, Usón, Isabel, Fisher, Jed F, Mobashery, Shahriar, Hermoso, Juan A
Format: Article
Language:English
Subjects:
Catalytic Domain
Cell Wall - metabolism
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli
Escherichia coli - cytology
Escherichia coli - metabolism
Escherichia coli Proteins - chemistry
Escherichia coli Proteins - genetics
Escherichia coli Proteins - metabolism
Glycosyltransferases - chemistry
Glycosyltransferases - metabolism
Models, Molecular
Mutation
Peptidoglycan - chemistry
Protein Conformation
Protein Structure, Tertiary
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Summary:The lytic transglycosylases are essential bacterial enzymes that catalyze the nonhydrolytic cleavage of the glycan strands of the bacterial cell wall. We describe here the structural and catalytic properties of MltC, one of the seven lytic transglycosylases found in the genome of the Gram-negative bacterium Escherichia coli. The 2.3 Å resolution X-ray structure of a soluble construct of MltC shows a unique, compared to known lytic transglycosylase structures, two-domain structure characterized by an expansive active site of 53 Å length extending through an interface between the domains. The structures of three complexes of MltC with cell wall analogues suggest the positioning of the peptidoglycan in the active site both as a substrate and as a product. One complex is suggested to correspond to an intermediate in the course of sequential and exolytic cleavage of the peptidoglycan. Moreover, MltC partitioned its reactive oxocarbenium-like intermediate between trapping by the C6-hydroxyl of the muramyl moiety (lytic transglycosylase activity, the major path) and by water (muramidase activity). Genomic analysis identifies the presence of an MltC homologue in no less than 791 bacterial genomes. While the role of MltC in cell wall assembly and maturation remains uncertain, we propose a functional role for this enzyme as befits the uniqueness of its two-domain structure.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb500439c