4QSL
Crystal Structure of Listeria Monocytogenes Pyruvate Carboxylase
Summary for 4QSL
| Entry DOI | 10.2210/pdb4qsl/pdb |
| Related | 4QSH 4QSK |
| Descriptor | Pyruvate carboxylase (1 entity in total) |
| Functional Keywords | tim barrell, pyruvate carboxylase, acetyl-coa, biotin, ligase |
| Biological source | Listeria monocytogenes |
| Total number of polymer chains | 8 |
| Total formula weight | 1026061.75 |
| Authors | Choi, P.H.,Tong, L. (deposition date: 2014-07-04, release date: 2014-10-29, Last modification date: 2023-09-20) |
| Primary citation | Sureka, K.,Choi, P.H.,Precit, M.,Delince, M.,Pensinger, D.A.,Huynh, T.N.,Jurado, A.R.,Goo, Y.A.,Sadilek, M.,Iavarone, A.T.,Sauer, J.D.,Tong, L.,Woodward, J.J. The Cyclic Dinucleotide c-di-AMP Is an Allosteric Regulator of Metabolic Enzyme Function. Cell(Cambridge,Mass.), 158:1389-1401, 2014 Cited by PubMed 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 Å 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. PubMed: 25215494DOI: 10.1016/j.cell.2014.07.046 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.28 Å) |
Structure validation
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