4QSK

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

4QSK の概要

• エントリーDOI: 10.2210/pdb4qsk/pdb
• 関連するPDBエントリー: 4QSH 4QSL
• 分子名称: Pyruvate carboxylase, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide, CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: tim barrel, pyruvate carboxylase, acetyl-coa, biotin, ligase
• 由来する生物種: Listeria monocytogenes
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 258582.71

構造登録者

Choi, P.H.,Tong, L. (登録日: 2014-07-04, 公開日: 2014-10-29, 最終更新日: 2023-09-20)

主引用文献

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

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: 25215494
DOI: 10.1016/j.cell.2014.07.046

実験手法

X-RAY DIFFRACTION (2.7 Å)