PDBsum entry: 3fi7

Hydrolase

PDB id: 3fi7

Contents

Protein chain

177 a.a. *

Ligands

SO4

Waters ×158

* Residue conservation analysis

PDB id:

3fi7

Name:

Hydrolase

Title:

Crystal structure of the autolysin auto (lmo1076) from liste monocytogenes, catalytic domain

Structure:

Lmo1076 protein. Chain: a. Fragment: fused residues 52-71 and 84-243. Engineered: yes. Other_details: a fusion of three non-physiological residues lmo1076 52-71, lmo1076 84-243

Source:

Undefined, listeria monocytogenes. Organism_taxid: 32644, 1639. Strain: egd-e. Gene: lmo1076. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.35Å R-factor: 0.181 R-free: 0.204

Authors:

M.Bublitz,L.Polle,C.Holland,M.Nimtz,D.W.Heinz,W.D.Schubert

Key ref:

M.Bublitz et al. (2009). Structural basis for autoinhibition and activation of Auto, a virulence-associated peptidoglycan hydrolase of Listeria monocytogenes. Mol Microbiol, 71, 1509-1522. PubMed id: 19210622 DOI: 10.1111/j.1365-2958.2009.06619.x

Date:

11-Dec-08 Release date: 07-Apr-09

Protein chain

Q8Y842  (Q8Y842_LISMO) -  Lmo1076 protein

Seq: 572 a.a.

Struc: 177 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: cellular cell wall macromolecule metabolic process (2 terms)
• Biochemical function: hydrolase activity (2 terms)

DOI no: 10.1111/j.1365-2958.2009.06619.x

Mol Microbiol 71:1509-1522 (2009)

PubMed id: 19210622

Structural basis for autoinhibition and activation of Auto, a virulence-associated peptidoglycan hydrolase of Listeria monocytogenes.

M.Bublitz, L.Polle, C.Holland, D.W.Heinz, M.Nimtz, W.D.Schubert.

ABSTRACT

During a bacterial infection, each successive step is orchestrated by a dedicated set of virulence factors. In Gram-positive bacteria, the presentation or release of such factors is crucially dependent on the continual remodelling of the cell wall. We have investigated the autolysin or peptidoglycan hydrolase Auto (Lmo1076) from the human pathogen Listeria monocytogenes to structurally and biochemically underpin its role in host cell invasion. We demonstrate that Auto is an N-acetylglucosaminidase, that it is autoinhibited when newly secreted but activated by proteolytic cleavage, that it has an acidic pH optimum and that it preferentially cleaves acetylated over de-acetylated peptidoglycan. The crystal structure of Auto, the first for glycoside hydrolase family 73, and the first for a listerial autolysin, indicates that autoinhibition is due to an N-terminal alpha-helix unique to Auto that physically blocks the substrate-binding cleft. We identify Glu122 and Glu156 as the two catalytically essential carboxylate groups. The physical properties of Auto as well as its localization to lipoteichoic acid by its four C-terminal GW modules imply cell wall degradation by Auto to be highly co-ordinated. Its spatio-temporally controlled activation and localized activity in an acidified environment indicate that it facilitates remodelling of the cell wall and may be involved in co-ordinating the release of virulence factors at specific stages of an infection.