4s1c

Crystal Structure of L. monocytogenes phosphodiesterase PgpH HD domain

spinqualitylabelsall models 4s1c, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4s1c is a 2 chain structure with sequence from Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8Y746_LISMO Publication Abstract from PubMed 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. An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence.,Huynh TN, Luo S, Pensinger D, Sauer JD, Tong L, Woodward JJ Proc Natl Acad Sci U S A. 2015 Jan 12. pii: 201416485. PMID:25583510 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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