4qsk

Crystal Structure of L. monocytogenes Pyruvate Carboxylase in complex with Cyclic-di-AMP

spinqualitylabelsall models 4qsk, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qsk is a 2 chain structure with sequence from Listeria monocytogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: 2BA, FLC, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function.,Sureka K, Choi PH, Precit M, Delince M, Pensinger DA, Huynh TN, Jurado AR, Goo YA, Sadilek M, Iavarone AT, Sauer JD, Tong L, Woodward JJ Cell. 2014 Sep 11;158(6):1389-401. doi: 10.1016/j.cell.2014.07.046. PMID:25215494 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate carboxylase 3D structures

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