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Title: Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori

Abstract

Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on alarmones, guanosine pentaphosphate (pppGpp), and tetraphosphate (ppGpp), to regulate global gene expression. The ppGpp is more potent than pppGpp in the regulatory activity, and pppGpp phosphohydrolase (GppA) plays a key role in (p)ppGpp homeostasis. Sharing a similar domain structure, GppA is indistinguishable from exopolyphosphatase (PPX), which mediates the metabolism of cellular inorganic polyphosphate. Here, our phylogenetic analysis of PPX/GppA homologs in bacteria shows a wide distribution with several distinct subfamilies, and our structural and functional analysis of Escherichia coli GppA and Helicobacter pylori PPX/GppA reveals unique properties of each homolog. These results explain how each homolog possesses its distinct functionality.

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [2]; ORCiD logo [1]
  1. Macromolecular Crystallography Laboratory National Cancer Institute Frederick MD USA
  2. RNA Biology Laboratory National Cancer Institute Frederick MD USA
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1575312
Grant/Contract Number:  
DE‐AC02‐06CH11357
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
Federation of European Biochemical Societies (FEBS) Journal
Additional Journal Information:
Journal Name: Federation of European Biochemical Societies (FEBS) Journal Journal Volume: 287 Journal Issue: 9; Journal ID: ISSN 1742-464X
Publisher:
Wiley-Blackwell
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Song, He, Dharmasena, Madushini N., Wang, Chao, Shaw, Gary X., Cherry, Scott, Tropea, Joseph E., Jin, Ding J., and Ji, Xinhua. Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori. United Kingdom: N. p., 2019. Web. doi:10.1111/febs.15120.
Song, He, Dharmasena, Madushini N., Wang, Chao, Shaw, Gary X., Cherry, Scott, Tropea, Joseph E., Jin, Ding J., & Ji, Xinhua. Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori. United Kingdom. https://doi.org/10.1111/febs.15120
Song, He, Dharmasena, Madushini N., Wang, Chao, Shaw, Gary X., Cherry, Scott, Tropea, Joseph E., Jin, Ding J., and Ji, Xinhua. Sat . "Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori". United Kingdom. https://doi.org/10.1111/febs.15120.
@article{osti_1575312,
title = {Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori},
author = {Song, He and Dharmasena, Madushini N. and Wang, Chao and Shaw, Gary X. and Cherry, Scott and Tropea, Joseph E. and Jin, Ding J. and Ji, Xinhua},
abstractNote = {Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on alarmones, guanosine pentaphosphate (pppGpp), and tetraphosphate (ppGpp), to regulate global gene expression. The ppGpp is more potent than pppGpp in the regulatory activity, and pppGpp phosphohydrolase (GppA) plays a key role in (p)ppGpp homeostasis. Sharing a similar domain structure, GppA is indistinguishable from exopolyphosphatase (PPX), which mediates the metabolism of cellular inorganic polyphosphate. Here, our phylogenetic analysis of PPX/GppA homologs in bacteria shows a wide distribution with several distinct subfamilies, and our structural and functional analysis of Escherichia coli GppA and Helicobacter pylori PPX/GppA reveals unique properties of each homolog. These results explain how each homolog possesses its distinct functionality.},
doi = {10.1111/febs.15120},
journal = {Federation of European Biochemical Societies (FEBS) Journal},
number = 9,
volume = 287,
place = {United Kingdom},
year = {2019},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1111/febs.15120

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Cited by: 13 works
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Works referenced in this record:

Recent functional insights into the role of (p)ppGpp in bacterial physiology
journal, April 2015

  • Hauryliuk, Vasili; Atkinson, Gemma C.; Murakami, Katsuhiko S.
  • Nature Reviews Microbiology, Vol. 13, Issue 5
  • DOI: 10.1038/nrmicro3448

Uniqueness of ab initio shape determination in small-angle scattering
journal, April 2003

  • Volkov, Vladimir V.; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 36, Issue 3, p. 860-864
  • DOI: 10.1107/S0021889803000268

eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences
journal, November 2015

  • Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer
  • Nucleic Acids Research, Vol. 44, Issue D1
  • DOI: 10.1093/nar/gkv1248

Hit the right spots: cell cycle control by phosphorylated guanosines in alphaproteobacteria
journal, January 2017

  • Hallez, Régis; Delaby, Marie; Sanselicio, Stefano
  • Nature Reviews Microbiology, Vol. 15, Issue 3
  • DOI: 10.1038/nrmicro.2016.183

Novel Assay Reveals Multiple Pathways Regulating Stress-Induced Accumulations of Inorganic Polyphosphate in Escherichia coli
journal, April 1998


A Magic Spot in Genome Maintenance
journal, January 2017


Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard
journal, December 2007

  • Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1
  • DOI: 10.1107/S090744490705024X

CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates
journal, December 1995

  • Svergun, D.; Barberato, C.; Koch, M. H. J.
  • Journal of Applied Crystallography, Vol. 28, Issue 6
  • DOI: 10.1107/S0021889895007047

Determination of the regularization parameter in indirect-transform methods using perceptual criteria
journal, August 1992


ppGpp couples transcription to DNA repair in E. coli
journal, May 2016


Guanosine pentaphosphate phosphohydrolase of Escherichia coli is a long-chain exopolyphosphatase.
journal, August 1993

  • Keasling, J. D.; Bertsch, L.; Kornberg, A.
  • Proceedings of the National Academy of Sciences, Vol. 90, Issue 15
  • DOI: 10.1073/pnas.90.15.7029

Functional characterization of exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) of Campylobacter jejuni
journal, February 2014

  • Malde, Anandkumar; Gangaiah, Dharanesh; Chandrashekhar, Kshipra
  • Virulence, Vol. 5, Issue 4
  • DOI: 10.4161/viru.28311

A polyphosphate kinase (PPK2) widely conserved in bacteria
journal, December 2002

  • Zhang, H.; Ishige, K.; Kornberg, A.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 26
  • DOI: 10.1073/pnas.262655199

PRIMUS: a Windows PC-based system for small-angle scattering data analysis
journal, September 2003

  • Konarev, Petr V.; Volkov, Vladimir V.; Sokolova, Anna V.
  • Journal of Applied Crystallography, Vol. 36, Issue 5, p. 1277-1282
  • DOI: 10.1107/S0021889803012779

Bacterial nucleotide-based second messengers
journal, April 2009


Inorganic Polyphosphate: A Molecule of Many Functions
journal, June 1999


Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
journal, May 2009

  • Terwilliger, Thomas C.; Adams, Paul D.; Read, Randy J.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 6
  • DOI: 10.1107/S0907444909012098

The magic dance of the alarmones (p)ppGpp: The structural biology of the alarmones (p)ppGpp
journal, June 2016

  • Steinchen, Wieland; Bange, Gert
  • Molecular Microbiology, Vol. 101, Issue 4
  • DOI: 10.1111/mmi.13412

Inorganic Polyphosphate: Essential for Growth and Survival
journal, June 2009


Guanosine Tetra- and Pentaphosphate Promote Accumulation of Inorganic Polyphosphate in Escherichia coli
journal, August 1997

  • Kuroda, Akio; Murphy, Helen; Cashel, Michael
  • Journal of Biological Chemistry, Vol. 272, Issue 34
  • DOI: 10.1074/jbc.272.34.21240

Structural Characterization of the Stringent Response Related Exopolyphosphatase/Guanosine Pentaphosphate Phosphohydrolase Protein Family ,
journal, July 2004

  • Kristensen, Ole; Laurberg, Martin; Liljas, Anders
  • Biochemistry, Vol. 43, Issue 28
  • DOI: 10.1021/bi049083c

ExPASy: the proteomics server for in-depth protein knowledge and analysis
journal, July 2003


The complete genome of the hyperthermophilic bacterium Aquifex aeolicus
journal, March 1998

  • Deckert, Gerard; Warren, Patrick V.; Gaasterland, Terry
  • Nature, Vol. 392, Issue 6674
  • DOI: 10.1038/32831

Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees
journal, April 2016

  • Letunic, Ivica; Bork, Peer
  • Nucleic Acids Research, Vol. 44, Issue W1
  • DOI: 10.1093/nar/gkw290

The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X
journal, July 2019


Direct binding targets of the stringent response alarmone (p)ppGpp
journal, August 2012


HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes
journal, July 2006

  • Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek
  • Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8
  • DOI: 10.1107/S0907444906019949

Coot model-building tools for molecular graphics
journal, November 2004

  • Emsley, Paul; Cowtan, Kevin
  • Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
  • DOI: 10.1107/S0907444904019158

Structure of the PPX/GPPA Phosphatase from Aquifex aeolicus in Complex with the Alarmone ppGpp
journal, February 2008

  • Kristensen, Ole; Ross, Birthe; Gajhede, Michael
  • Journal of Molecular Biology, Vol. 375, Issue 5
  • DOI: 10.1016/j.jmb.2007.11.073

New developments in the ATSAS program package for small-angle scattering data analysis
journal, March 2012

  • Petoukhov, Maxim V.; Franke, Daniel; Shkumatov, Alexander V.
  • Journal of Applied Crystallography, Vol. 45, Issue 2
  • DOI: 10.1107/S0021889812007662

Living dangerously: how Helicobacter pylori survives in the human stomach
journal, June 2001

  • Montecucco, Cesare; Rappuoli, Rino
  • Nature Reviews Molecular Cell Biology, Vol. 2, Issue 6
  • DOI: 10.1038/35073084

Helicobacter pylori Initiates the Stringent Response upon Nutrient and pH Downshift
journal, May 2006


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

The Functional Cycle of Rnt1p: Five Consecutive Steps of Double-Stranded RNA Processing by a Eukaryotic RNase III
journal, February 2017


Automated matching of high- and low-resolution structural models
journal, February 2001


The Structure of the Exopolyphosphatase (PPX) from Escherichia coli O157:H7 Suggests a Binding Mode for Long Polyphosphate Chains
journal, June 2006

  • Rangarajan, Erumbi S.; Nadeau, Guy; Li, Yunge
  • Journal of Molecular Biology, Vol. 359, Issue 5
  • DOI: 10.1016/j.jmb.2006.04.031

An exopolyphosphatase of Escherichia coli. The enzyme and its ppx gene in a polyphosphate operon.
journal, January 1993


Determination of the molecular weight of proteins in solution from a single small-angle X-ray scattering measurement on a relative scale
journal, December 2009

  • Fischer, H.; de Oliveira Neto, M.; Napolitano, H. B.
  • Journal of Applied Crystallography, Vol. 43, Issue 1
  • DOI: 10.1107/S0021889809043076

(p)ppGpp: Still Magical?
journal, October 2008


Preparation of selenomethionyl proteins for phase determination
book, January 1997


The Protein Data Bank
journal, January 2000


Differential regulation by ppGpp versus pppGpp in Escherichia coli
journal, April 2013

  • Mechold, Undine; Potrykus, Katarzyna; Murphy, Helen
  • Nucleic Acids Research, Vol. 41, Issue 12
  • DOI: 10.1093/nar/gkt302

Origin of Exopolyphosphatase Processivity: Fusion of an ASKHA Phosphotransferase and a Cyclic Nucleotide Phosphodiesterase Homolog
journal, August 2006


Jalview Version 2--a multiple sequence alignment editor and analysis workbench
journal, January 2009


Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206