4S1C

Crystal Structure of L. monocytogenes phosphodiesterase PgpH HD domain

4S1C の概要

• エントリーDOI: 10.2210/pdb4s1c/pdb
• 関連するPDBエントリー: 4S1B
• 分子名称: Lmo1466 protein, FE (III) ION (3 entities in total)
• 機能のキーワード: c-di-amp, listeria monocytogenes, phosphodiesterase, hd domain, hydrolase
• 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: 50468.99

構造登録者

Luo, S.,Tong, L. (登録日: 2015-01-12, 公開日: 2015-02-11, 最終更新日: 2024-02-28)

主引用文献

Huynh, T.N.,Luo, S.,Pensinger, D.,Sauer, J.D.,Tong, L.,Woodward, J.J.
An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence.
Proc.Natl.Acad.Sci.USA, 112:E747-E756, 2015

PubMed Abstract: The nucleotide cyclic di-3',5'- adenosine monophosphate (c-di-AMP) was recently identified as an essential and widespread second messenger in bacterial signaling. Among c-di-AMP-producing bacteria, altered nucleotide levels result in several physiological defects and attenuated virulence. Thus, a detailed molecular understanding of c-di-AMP metabolism is of both fundamental and practical interest. Currently, c-di-AMP degradation is recognized solely among DHH-DHHA1 domain-containing phosphodiesterases. Using chemical proteomics, we identified the Listeria monocytogenes protein PgpH as a molecular target of c-di-AMP. Biochemical and structural studies revealed that the PgpH His-Asp (HD) domain bound c-di-AMP with high affinity and specifically hydrolyzed this nucleotide to 5'-pApA. PgpH hydrolysis activity was inhibited by ppGpp, indicating a cross-talk between c-di-AMP signaling and the stringent response. Genetic analyses supported coordinated regulation of c-di-AMP levels in and out of the host. Intriguingly, a L. monocytogenes mutant that lacks c-di-AMP phosphodiesterases exhibited elevated c-di-AMP levels, hyperinduced a host type-I IFN response, and was significantly attenuated for infection. Furthermore, PgpH homologs, which belong to the 7TMR-HD family, are widespread among hundreds of c-di-AMP synthesizing microorganisms. Thus, PgpH represents a broadly conserved class of c-di-AMP phosphodiesterase with possibly other physiological functions in this crucial signaling network.

PubMed: 25583510
DOI: 10.1073/pnas.1416485112

実験手法

X-RAY DIFFRACTION (2.398 Å)