PDBsum entry 5ug1

Transferase

PDB id: 5ug1

Contents

Protein chain

179 a.a.

Ligands

03S

Metals

_NA

Waters ×156

PDB id:

5ug1

Name:

Transferase

Title:

Structure of streptococcus pneumoniae peptidoglycan o- acetyltransferase a (oata) c-terminal catalytic domain with methylsulfonyl adduct

Structure:

Acyltransferase. Chain: a. Engineered: yes. Mutation: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Gene: oata_2, oata, ers020148_01611, ers021300_00524, ers022045_04974. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.10Å R-factor: 0.179 R-free: 0.235

Authors:

D.Sychantha,C.Jones,D.J.Little,P.J.Moynihan,H.Robinson,N.F.Galley, D.I.Roper,C.G.Dowson,P.L.Howell,A.J.Clarke

Key ref:

D.Sychantha et al. (2017). In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA). PLoS Pathog, 13, e1006667. PubMed id: 29077761

Date:

06-Jan-17 Release date: 25-Oct-17

Protein chain

Q8CY83  (Q8CY83_STRR6) -  Acyltransferase 3 domain-containing protein from Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Seq: 605 a.a.

Struc: 179 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.- - ?????

PLoS Pathog 13:e1006667 (2017)

PubMed id: 29077761

In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA).

D.Sychantha, C.S.Jones, D.J.Little, P.J.Moynihan, H.Robinson, N.F.Galley, D.I.Roper, C.G.Dowson, P.L.Howell, A.J.Clarke.

ABSTRACT

The O-acetylation of the essential cell wall polymer peptidoglycan occurs in most Gram-positive bacterial pathogens, including species of Staphylococcus, Streptococcus and Enterococcus. This modification to peptidoglycan protects these pathogens from the lytic action of the lysozymes of innate immunity systems and, as such, is recognized as a virulence factor. The key enzyme involved, peptidoglycan O-acetyltransferase A (OatA) represents a particular challenge to biochemical study since it is a membrane associated protein whose substrate is the insoluble peptidoglycan cell wall polymer. OatA is predicted to be bimodular, being comprised of an N-terminal integral membrane domain linked to a C-terminal extracytoplasmic domain. We present herein the first biochemical and kinetic characterization of the C-terminal catalytic domain of OatA from two important human pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Using both pseudosubstrates and novel biosynthetically-prepared peptidoglycan polymers, we characterized distinct substrate specificities for the two enzymes. In addition, the high resolution crystal structure of the C-terminal domain reveals an SGNH/GDSL-like hydrolase fold with a catalytic triad of amino acids but with a non-canonical oxyanion hole structure. Site-specific replacements confirmed the identity of the catalytic and oxyanion hole residues. A model is presented for the O-acetylation of peptidoglycan whereby the translocation of acetyl groups from a cytoplasmic source across the cytoplasmic membrane is catalyzed by the N-terminal domain of OatA for their transfer to peptidoglycan by its C-terminal domain. This study on the structure-function relationship of OatA provides a molecular and mechanistic understanding of this bacterial resistance mechanism opening the prospect for novel chemotherapeutic exploration to enhance innate immunity protection against Gram-positive pathogens.