pasta domain
Recently Published Documents


TOTAL DOCUMENTS

10
(FIVE YEARS 0)

H-INDEX

7
(FIVE YEARS 0)

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sabrina Wamp ◽  
Zoe J Rutter ◽  
Jeanine Rismondo ◽  
Claire E Jennings ◽  
Lars Möller ◽  
...  

Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogen Listeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.


2019 ◽  
Author(s):  
Sabrina Wamp ◽  
Zoe J. Rutter ◽  
Jeanine Rismondo ◽  
Claire E. Jennings ◽  
Lars Möller ◽  
...  

ABSTRACTPeptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that sense PG fragments. However, only a few PG biosynthetic enzymes are direct kinase substrates. Here, we identify the conserved ReoM protein as a novel PASTA-eSTK substrate in the Gram-positive pathogen Listeria monocytogenes. Our data show that the phosphorylation of ReoM is essential as it controls ClpCP-dependent proteolytic degradation of the essential enzyme MurA, which catalyses the first committed step in PG biosynthesis. We also identify ReoY as a second novel factor required for degradation of ClpCP substrates. Collectively, our data imply that the first committed step of PG biosynthesis is activated through control of ClpCP protease activity in response to signals of PG homeostasis imbalance.


Open Biology ◽  
2015 ◽  
Vol 5 (7) ◽  
pp. 150025 ◽  
Author(s):  
Obolbek Turapov ◽  
Jessica Loraine ◽  
Christopher H. Jenkins ◽  
Philippe Barthe ◽  
Daniel McFeely ◽  
...  

PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis , and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture.


2014 ◽  
Vol 58 (8) ◽  
pp. 4486-4494 ◽  
Author(s):  
Daniel A. Pensinger ◽  
Matthew T. Aliota ◽  
Adam J. Schaenzer ◽  
Kyle M. Boldon ◽  
Israr-ul H. Ansari ◽  
...  

ABSTRACTWhile β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of thepenicillin binding proteinandserine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistantStaphylococcus aureus(MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase inListeria monocytogenesby the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase ofL. monocytogenes(PrkA). Importantly, staurosporine did not inhibit aL. monocytogeneskinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization ofL. monocytogenesto β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics.


Biopolymers ◽  
2014 ◽  
Vol 101 (7) ◽  
pp. 712-719 ◽  
Author(s):  
Luisa Calvanese ◽  
Lucia Falcigno ◽  
Cira Maglione ◽  
Daniela Marasco ◽  
Alessia Ruggiero ◽  
...  

2010 ◽  
Vol 404 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Patricia Paracuellos ◽  
Allison Ballandras ◽  
Xavier Robert ◽  
Richard Kahn ◽  
Mireille Hervé ◽  
...  

Structure ◽  
2010 ◽  
Vol 18 (5) ◽  
pp. 606-615 ◽  
Author(s):  
Philippe Barthe ◽  
Galina V. Mukamolova ◽  
Christian Roumestand ◽  
Martin Cohen-Gonsaud

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 932-943 ◽  
Author(s):  
Cédric Absalon ◽  
Michal Obuchowski ◽  
Edwige Madec ◽  
Delphine Delattre ◽  
I. Barry Holland ◽  
...  

The conserved prpC, prkC, cpgA locus in Bacillus subtilis encodes respectively a Ser/Thr phosphatase, the cognate sensor kinase (containing an external PASTA domain suggested to bind peptidoglycan precursors) and CpgA, a small ribosome-associated GTPase that we have shown previously is implicated in shape determination and peptidoglycan deposition. In this study, in a search for targets of PrkC and PrpC, we showed that, in vitro, CpgA itself is phosphorylated on serine and threonine, and another GTPase, the translation factor EF-Tu, is also phosphorylated by the kinase on the conserved T384 residue. Both substrates are dephosphorylated by PrpC in vitro. In addition, we identified YezB, a 10.3 kDa polypeptide, and a component of the stressosome, as a substrate for both enzymes in vitro and apparently in vivo. We propose that the PrpC/PrkC/CpgA system constitutes an important element of a regulatory network involved in the coordination of cell wall expansion and growth in B. subtilis.


2002 ◽  
Vol 27 (9) ◽  
pp. 438-440 ◽  
Author(s):  
Corin Yeats ◽  
Robert D Finn ◽  
Alex Bateman
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document