4QSH: Crystal Structure Of L. Monocytogenes Pyruvate Carboxylase In Complex With Cyclic-di-amp

Citation:
Abstract
Cyclic di-adenosine monophosphate (c-di-AMP) is a broadly conserved second messenger required for bacterial growth and infection. However, the molecular mechanisms of c-di-AMP signaling are still poorly understood. Using a chemical proteomics screen for c-di-AMP-interacting proteins in the pathogen Listeria monocytogenes, we identified several broadly conserved protein receptors, including the central metabolic enzyme pyruvate carboxylase (LmPC). Biochemical and crystallographic studies of the LmPC-c-di-AMP interaction revealed a previously unrecognized allosteric regulatory site 25 A from the active site. Mutations in this site disrupted c-di-AMP binding and affected catalytic activity of LmPC as well as PC from pathogenic Enterococcus faecalis. C-di-AMP depletion resulted in altered metabolic activity in L. monocytogenes. Correction of this metabolic imbalance rescued bacterial growth, reduced bacterial lysis, and resulted in enhanced bacterial burdens during infection. These findings greatly expand the c-di-AMP signaling repertoire and reveal a central metabolic regulatory role for a cyclic dinucleotide.
PDB ID: 4QSHDownload
MMDB ID: 124360
PDB Deposition Date: 2014/7/4
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.51  Å
Source Organism:
Similar Structures:
Biological Unit for 4QSH: tetrameric; determined by author and by software (PISA)
Molecular Components in 4QSH
Label Count Molecule
Proteins (4 molecules)
4
Pyruvate Carboxylase
Molecule annotation
Chemicals (11 molecules)
1
4
2
4
3
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.