PDBsum entry 6be0

Transferase

PDB id: 6be0

Contents

Protein chain

266 a.a.

Ligands

IHP

COA

Waters ×65

PDB id:

6be0

Name:

Transferase

Title:

Avra dell154 with ip6, coa

Structure:

Avra. Chain: a. Engineered: yes

Source:

Salmonella typhimurium (strain 4/74). Organism_taxid: 909946. Strain: 4/74. Gene: avra, stm474_3004. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.44Å R-factor: 0.189 R-free: 0.231

Authors:

J.M.Labriola,B.Nagar

Key ref:

J.M.Labriola et al. (2018). Structural Analysis of the Bacterial Effector AvrA Identifies a Critical Helix Involved in Substrate Recognition. Biochemistry, 57, 4985-4996. PubMed id: 30025209 DOI: 10.1021/acs.biochem.8b00512

Date:

24-Oct-17 Release date: 01-Aug-18

Protein chain

E8XKZ3  (E8XKZ3_SALT4) -  AvrA from Salmonella typhimurium (strain 4/74)

Seq: 301 a.a.

Struc: 266 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/acs.biochem.8b00512

Biochemistry 57:4985-4996 (2018)

PubMed id: 30025209

Structural Analysis of the Bacterial Effector AvrA Identifies a Critical Helix Involved in Substrate Recognition.

J.M.Labriola, Y.Zhou, B.Nagar.

ABSTRACT

Bacterial effector proteins are essential for the infection and proliferation of pathogenic bacteria through manipulation of host immune response pathways. AvrA is a Salmonella effector that belongs to the YopJ family of acetyltransferases, which suppresses c-JUN N-terminal kinase (JNK) signaling in mammals through acetylation of mitogen-activated receptor kinase kinases 4 and 7 (MKK4/7). Interestingly, there are two paralogues of AvrA that differ by only a single internal leucine residue, which when absent (AvrA^ΔL140) abrogates the ability to suppress JNK signaling. Here, we present the first crystal structure of a bacterial effector from an animal pathogen, AvrA^ΔL140, accompanied by a thorough biophysical characterization of both AvrA variants. The structure in complex with inositol hexaphosphate and coenzyme A reveals two closely associated domains consisting of a catalytic core that resembles the CE clan peptidases and a wedge-shaped regulatory region that mediates cofactor and substrate binding. The loss of the putative function of AvrA^ΔL140 is due to its inability to interact with MKK4/7, which ultimately arises from an altered conformation of a critical helix adjacent to the active site that harbors L140. These results provide general insights into substrate recognition across the YopJ family of acetyltransferases.