PDBsum entry 5ep1

Transcription

PDB id: 5ep1

Contents

Protein chain

252 a.a.

Ligands

ACT ×4

Waters ×221

PDB id:

5ep1

Name:

Transcription

Title:

Quorum-sensing signal integrator luxo - catalytic domain

Structure:

Putative repressor protein luxo. Chain: a. Fragment: aaa+ catalytic domain (unp residues 141-387). Engineered: yes

Source:

Photobacterium angustum. Organism_taxid: 661. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.50Å R-factor: 0.163 R-free: 0.183

Authors:

T.Shah,H.B.Selcuk,P.D.Jeffrey,F.M.Hughson

Key ref:

H.Boyaci et al. (2016). Structure, Regulation, and Inhibition of the Quorum-Sensing Signal Integrator LuxO. Plos Biol, 14, e1002464. PubMed id: 27219477 DOI: 10.1371/journal.pbio.1002464

Date:

11-Nov-15 Release date: 20-Apr-16

Protein chain

Q1ZS18  (Q1ZS18_PHOAS) -  Putative repressor protein luxO from Photobacterium angustum (strain S14 / CCUG 15956)

Seq: 480 a.a.

Struc: 252 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1371/journal.pbio.1002464

Plos Biol 14:e1002464 (2016)

PubMed id: 27219477

Structure, Regulation, and Inhibition of the Quorum-Sensing Signal Integrator LuxO.

H.Boyaci, T.Shah, A.Hurley, B.Kokona, Z.Li, C.Ventocilla, P.D.Jeffrey, M.F.Semmelhack, R.Fairman, B.L.Bassler, F.M.Hughson.

ABSTRACT

In a process called quorum sensing, bacteria communicate with chemical signal molecules called autoinducers to control collective behaviors. In pathogenic vibrios, including Vibrio cholerae, the accumulation of autoinducers triggers repression of genes responsible for virulence factor production and biofilm formation. The vibrio autoinducer molecules bind to transmembrane receptors of the two-component histidine sensor kinase family. Autoinducer binding inactivates the receptors' kinase activities, leading to dephosphorylation and inhibition of the downstream response regulator LuxO. Here, we report the X-ray structure of LuxO in its unphosphorylated, autoinhibited state. Our structure reveals that LuxO, a bacterial enhancer-binding protein of the AAA+ ATPase superfamily, is inhibited by an unprecedented mechanism in which a linker that connects the catalytic and regulatory receiver domains occupies the ATPase active site. The conformational change that accompanies receiver domain phosphorylation likely disrupts this interaction, providing a mechanistic rationale for LuxO activation. We also determined the crystal structure of the LuxO catalytic domain bound to a broad-spectrum inhibitor. The inhibitor binds in the ATPase active site and recapitulates elements of the natural regulatory mechanism. Remarkably, a single inhibitor molecule may be capable of inhibiting an entire LuxO oligomer.