Dataset Information

Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from Acinetobacter baumannii.

ABSTRACT: Peptidoglycan digestion by murein-degrading enzymes is a critical process in bacterial cell growth and/or cell division. The membrane-bound lytic murein transglycosylase A (MltA) is a murein-degrading enzyme; it catalyzes the cleavage of the β-1,4-glycosidic linkage between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans. Although substrate recognition and cleavage by MltA have been examined by previous structural and mutagenesis studies, the overall mechanism of MltA in conjunction with other functionally related molecules on the outer membrane of bacterial cells for peptidoglycan degradation has remained elusive. In this study, the crystal structure of MltA from the virulent human pathogen Acinetobacter baumannii is characterized and presented. The study indicated that MltA from A. baumannii forms homodimers via an extra domain which is specific to this species. Furthermore, the working mechanism of MltA with various functionally related proteins on the bacterial outer membrane was modeled based on the structural and biochemical analysis.

SUBMITTER: Jang H

PROVIDER: S-EPMC8562663 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from Acinetobacter baumannii.

Jang Hyunseok H Do Hackwon H Kim Chang Min CM Kim Gi Eob GE Lee Jun Hyuck JH Park Hyun Ho HH

IUCrJ 20210923 Pt 6

Peptidoglycan digestion by murein-degrading enzymes is a critical process in bacterial cell growth and/or cell division. The membrane-bound lytic murein transglycosylase A (MltA) is a murein-degrading enzyme; it catalyzes the cleavage of the β-1,4-glycosidic linkage between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans. Although substrate recognition and cleavage by MltA have been examined by previous structural and mutagenesis studies, the overall mechanism of Mlt ...[more]

PMID: 34804545

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Project description:Acinetobacter species are ubiquitous Gram-negative bacteria that can be found in water, in soil, and as commensals of the human skin. The successful inhabitation of Acinetobacter species in diverse environments is primarily attributable to the expression of an arsenal of stress resistance determinants, which includes an extensive repertoire of metal ion efflux systems. Metal ion homeostasis in the hospital pathogen Acinetobacter baumannii contributes to pathogenesis; however, insights into its metal ion transporters for environmental persistence are lacking. Here, we studied the impact of cadmium stress on A. baumannii. Our functional genomics and independent mutant analyses revealed a primary role for CzcE, a member of the cation diffusion facilitator (CDF) superfamily, in resisting cadmium stress. We also show that the CzcCBA heavy metal efflux system contributes to cadmium efflux. Collectively, these systems provide A. baumannii with a comprehensive cadmium translocation pathway from the cytoplasm to the periplasm and subsequently the extracellular space. Furthermore, analysis of the A. baumannii metallome under cadmium stress showed zinc depletion, as well as copper enrichment, both of which are likely to influence cellular fitness. Overall, this work provides new knowledge on the role of a broad arsenal of membrane transporters in A. baumannii metal ion homeostasis. IMPORTANCE Cadmium toxicity is a widespread problem, yet the interaction of this heavy metal with biological systems is poorly understood. Some microbes have evolved traits to proactively counteract cadmium toxicity, including Acinetobacter baumannii, which is notorious for persisting in harsh environments. Here, we show that A. baumannii utilizes a dedicated cadmium efflux protein in concert with a system that is primarily attuned to zinc efflux to efficiently overcome cadmium stress. The molecular characterization of A. baumannii under cadmium stress revealed how active cadmium efflux plays a key role in preventing the dysregulation of bacterial metal ion homeostasis, which appeared to be a primary means by which cadmium exerts toxicity upon the bacterium.

Dataset Information

Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from Acinetobacter baumannii.

Publications

Molecular basis of dimerization of lytic transglycosylase revealed by the crystal structure of MltA from <i>Acinetobacter baumannii</i>.

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