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C. Grangeasse - One of the best experts on this subject based on the ideXlab platform.
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Evolution of bacterial protein-tyrosine kinases and their relaxed specificity toward substrates
Genome Biology and Evolution, 2014Co-Authors: Lei Shi, C. Grangeasse, Lorena Kolar-znika, Ana Boskovic, Fanny Jadeau, Christophe Combet, Damjan Franjevic, Emmanuel Talla, Ivan MijakovicAbstract:It has often been speculated that bacterial protein-tyrosine kinases (BY-kinases) evolve rapidly and maintain relaxed substrate specificity to quickly adopt new substrates when evolutionary pressure in that direction arises. Here, we report a phylogenomic and biochemical analysis of BY-kinases, and their relationship to substrates aimed to validate this hypothesis. Our results suggest that BY-kinases are ubiquitously distributed in bacterial phyla and underwent a complex evolutionary history, affected considerably by gene duplications and horizontal gene transfer events. This is consistent with the fact that the BY-kinase sequences represent a high level of substitution saturation and have a higher evolutionary rate compared with other bacterial genes. On the basis of similarity networks, we could classify BY kinases into three main groups with 14 subgroups. Extensive sequence conservation was observed only around the three canonical Walker Motifs, whereas unique signatures proposed the functional speciation and diversification within some subgroups. The relationship between BY-kinases and their substrates was analyzed using a ubiquitous substrate (Ugd) and some Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence of coevolution between kinases and substrates at the sequence level was found. Seven BY-kinases, including well-characterized and previously uncharacterized ones, were used for experimental studies. Most of the tested kinases were able to phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite originating from very distant bacteria. Our results are consistent with the hypothesis that BY-kinases have evolved relaxed substrate specificity and are probably maintained as rapidly evolving platforms for adopting new substrates.
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Bacterial tyrosine-kinases: structure-function analysis and therapeutic potential.
Biochimica et Biophysica Acta, 2009Co-Authors: C. Grangeasse, Raphaël Terreux, Sylvie NesslerAbstract:Since the characterization of genes encoding Ser/Thr-kinases and Tyr-kinases in bacteria, in 1991 and 1997, respectively, a growing body of evidence has been reported showing the important role of these enzymes in the regulation of bacterial physiology. While most Ser/Thr-kinases share structural similarity with their eukaryotic counterparts, it seems that bacteria have developed their own Tyr-kinases to catalyze protein phosphorylation on tyrosine. Different types of Tyr-kinases have been identified in bacteria and a large number of them are similar to ATP-binding proteins with Walker Motifs. These enzymes have been grouped in the same family (BY-kinases) and the crystal structures of two of them have been recently characterized. Phosphoproteome analysis suggest that BY-kinases are involved in several cellular processes and to date, the best-characterized role of BY-kinases concerns the control of extracellular polysaccharide synthesis. Knowing the role of these compounds in the virulence of bacterial pathogens, BY-kinases can be considered as promising targets to combat some diseases. Here, we review the current knowledge on BY-kinases and discuss their potential for the development of new antibiotics.
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Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology
Trends in Biochemical Sciences, 2007Co-Authors: C. Grangeasse, Aj Cozzone, Josef Deutscher, Ivan MijakovicAbstract:Tyrosine phosphorylation is a key device in numerous cellular functions in eukaryotes, but in bacteria this protein modification was largely ignored until the mid-1990s. The first conclusive evidence of bacterial tyrosine phosphorylation came only a decade ago. Since then, several tyrosine kinases exhibiting unexpected features have been identified in a variety of bacteria. These enzymes use homologues of Walker Motifs of nucleotide-binding proteins for their catalytic mechanism, thus defining an idiosyncratic type of bacterial tyrosine kinases. Recently, bacterial tyrosine kinases have been found to phosphorylate an increasing list of endogenous protein substrates. This discovery contributes to the emerging picture that bacterial tyrosine phosphorylation is an important regulatory arsenal of bacterial physiology in addition to the classical serine/threonine kinases, and the 'two-component' and phosphotransferase systems.
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On the binding of ATP to the autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii.
FEBS Letters, 1999Co-Authors: P. Doublet, C. Vincent, C. Grangeasse, Aj Cozzone, B. DuclosAbstract:The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5′-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.
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On the binding of ATP to the autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii.
FEBS Letters, 1999Co-Authors: P. Doublet, C. Vincent, C. Grangeasse, Aj Cozzone, B. DuclosAbstract:The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5'-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5'-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.
Richard J. Lamont - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Tyrosine phosphorylation and bacterial virulence
2016Co-Authors: Sarah E. Whitmore, Richard J. LamontAbstract:Protein phosphorylation on tyrosine has emerged as a key device in the control of numerous cellular functions in bacteria. In this article, we review the structure and function of bacterial tyrosine kinases and phosphatases. Phosphorylation is catalyzed by autophosphorylating adenosine triphosphate-dependent enzymes (bacterial tyrosine (BY) kinases) that are characterized by the presence of Walker Motifs. The reverse reaction is catalyzed by three classes of enzymes: the eukaryotic-like phosphatases (PTPs) and dual-specific phosphatases; the low molecular weight protein-tyrosine phosphatases (LMW-PTPs); and the polymerase–histidinol phosphatases (PHP). Many BY kinases and tyrosine phosphatases can utilize host cell proteins as substrates, thereby contributing to bacterial pathogenicity. Bacterial tyrosine phosphorylation/dephosphorylation is also involved in biofilm formation and community development. The Porphyromonas gingivalis tyrosine phosphatase Ltp1 is involved in a restraint pathway that regulates heterotypic community development with Streptococcus gordonii. Ltp1 is upregulated by contact with S. gordonii and Ltp1 activity controls adhesin expression and levels of the interspecies signal AI-2
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Tyrosine phosphorylation and bacterial virulence
International Journal of Oral Science, 2012Co-Authors: Sarah E. Whitmore, Richard J. LamontAbstract:Tyrosine kinases and phosphatases are enzymes that regulate many bacterial proteins involved in promoting infection. Tyrosine kinases work by tacking phosphate molecules onto specific amino acids, while phosphatases take them off. Sarah Whitmore and Richard Lamont of the University of Louisville in Kentucky, USA, have now reviewed the structure and function of these enzymes, which contribute to bacterial virulence, including that of Porphyromonas gingivalis and Streptococcus gordonii . They explain that tyrosine kinases help regulate the production of specialized sugars that bacteria use to interact with target cells; many bacterial phosphatases, however, actively sabotage host cell signaling processes. The authors conclude that future work will provide a better understanding of these important enzymes and should help guide development of more effective antibacterial drugs. Protein phosphorylation on tyrosine has emerged as a key device in the control of numerous cellular functions in bacteria. In this article, we review the structure and function of bacterial tyrosine kinases and phosphatases. Phosphorylation is catalyzed by autophosphorylating adenosine triphosphate-dependent enzymes (bacterial tyrosine (BY) kinases) that are characterized by the presence of Walker Motifs. The reverse reaction is catalyzed by three classes of enzymes: the eukaryotic-like phosphatases (PTPs) and dual-specific phosphatases; the low molecular weight protein-tyrosine phosphatases (LMW-PTPs); and the polymerase–histidinol phosphatases (PHP). Many BY kinases and tyrosine phosphatases can utilize host cell proteins as substrates, thereby contributing to bacterial pathogenicity. Bacterial tyrosine phosphorylation/dephosphorylation is also involved in biofilm formation and community development. The Porphyromonas gingivalis tyrosine phosphatase Ltp1 is involved in a restraint pathway that regulates heterotypic community development with Streptococcus gordonii . Ltp1 is upregulated by contact with S. gordonii and Ltp1 activity controls adhesin expression and levels of the interspecies signal AI-2.
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Tyrosine phosphorylation and bacterial virulence.
International Journal of Oral Science, 2012Co-Authors: Sarah E. Whitmore, Richard J. LamontAbstract:Protein phosphorylation on tyrosine has emerged as a key device in the control of numerous cellular functions in bacteria. In this article, we review the structure and function of bacterial tyrosine kinases and phosphatases. Phosphorylation is catalyzed by autophosphorylating adenosine triphosphate-dependent enzymes (bacterial tyrosine (BY) kinases) that are characterized by the presence of Walker Motifs. The reverse reaction is catalyzed by three classes of enzymes: the eukaryotic-like phosphatases (PTPs) and dual-specific phosphatases; the low molecular weight protein-tyrosine phosphatases (LMW-PTPs); and the polymerase–histidinol phosphatases (PHP). Many BY kinases and tyrosine phosphatases can utilize host cell proteins as substrates, thereby contributing to bacterial pathogenicity. Bacterial tyrosine phosphorylation/dephosphorylation is also involved in biofilm formation and community development. The Porphyromonas gingivalis tyrosine phosphatase Ltp1 is involved in a restraint pathway that regulates heterotypic community development with Streptococcus gordonii. Ltp1 is upregulated by contact with S. gordonii and Ltp1 activity controls adhesin expression and levels of the interspecies signal AI-2.
Ivan Mijakovic - One of the best experts on this subject based on the ideXlab platform.
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Evolution of bacterial protein-tyrosine kinases and their relaxed specificity toward substrates
Genome Biology and Evolution, 2014Co-Authors: Lei Shi, C. Grangeasse, Lorena Kolar-znika, Ana Boskovic, Fanny Jadeau, Christophe Combet, Damjan Franjevic, Emmanuel Talla, Ivan MijakovicAbstract:It has often been speculated that bacterial protein-tyrosine kinases (BY-kinases) evolve rapidly and maintain relaxed substrate specificity to quickly adopt new substrates when evolutionary pressure in that direction arises. Here, we report a phylogenomic and biochemical analysis of BY-kinases, and their relationship to substrates aimed to validate this hypothesis. Our results suggest that BY-kinases are ubiquitously distributed in bacterial phyla and underwent a complex evolutionary history, affected considerably by gene duplications and horizontal gene transfer events. This is consistent with the fact that the BY-kinase sequences represent a high level of substitution saturation and have a higher evolutionary rate compared with other bacterial genes. On the basis of similarity networks, we could classify BY kinases into three main groups with 14 subgroups. Extensive sequence conservation was observed only around the three canonical Walker Motifs, whereas unique signatures proposed the functional speciation and diversification within some subgroups. The relationship between BY-kinases and their substrates was analyzed using a ubiquitous substrate (Ugd) and some Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence of coevolution between kinases and substrates at the sequence level was found. Seven BY-kinases, including well-characterized and previously uncharacterized ones, were used for experimental studies. Most of the tested kinases were able to phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite originating from very distant bacteria. Our results are consistent with the hypothesis that BY-kinases have evolved relaxed substrate specificity and are probably maintained as rapidly evolving platforms for adopting new substrates.
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Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology
Trends in Biochemical Sciences, 2007Co-Authors: C. Grangeasse, Aj Cozzone, Josef Deutscher, Ivan MijakovicAbstract:Tyrosine phosphorylation is a key device in numerous cellular functions in eukaryotes, but in bacteria this protein modification was largely ignored until the mid-1990s. The first conclusive evidence of bacterial tyrosine phosphorylation came only a decade ago. Since then, several tyrosine kinases exhibiting unexpected features have been identified in a variety of bacteria. These enzymes use homologues of Walker Motifs of nucleotide-binding proteins for their catalytic mechanism, thus defining an idiosyncratic type of bacterial tyrosine kinases. Recently, bacterial tyrosine kinases have been found to phosphorylate an increasing list of endogenous protein substrates. This discovery contributes to the emerging picture that bacterial tyrosine phosphorylation is an important regulatory arsenal of bacterial physiology in addition to the classical serine/threonine kinases, and the 'two-component' and phosphotransferase systems.
Beate Averhoff - One of the best experts on this subject based on the ideXlab platform.
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Functional dissection of the three N-terminal general secretory pathway domains and the Walker Motifs of the traffic ATPase PilF from Thermus thermophilus
Extremophiles, 2018Co-Authors: Kerstin Kruse, Ralf Salzer, Friederike Joos, Beate AverhoffAbstract:The traffic ATPase PilF of Thermus thermophilus powers pilus assembly as well as uptake of DNA. PilF differs from other traffic ATPases by a triplicated general secretory pathway II, protein E, N-terminal domain (GSPIIABC). We investigated the in vivo and in vitro roles of the GSPII domains, the Walker A motif and a catalytic glutamate by analyzing a set of PilF deletion derivatives and pilF mutants. Here, we report that PilF variants devoid of the first two or all three GSPII domains do not form stable hexamers indicating a role of the triplicated GSPII domain in complex formation and/or stability. A pilFΔGSPIIC mutant was significantly impaired in piliation which leads to the conclusion that the GSPIIC domain plays a vital role in pilus assembly. Interestingly, the pilFΔGSPIIC mutant was hypertransformable. This suggests that GSPIIC strongly affects transformation efficiency. A pilF∆GSPIIA mutant exhibited wild-type piliation but reduced pilus-mediated twitching motility, suggesting that GSPIIA plays a role in pilus dynamics. Furthermore, we report that pilF mutants with a defect in the ATP binding Walker A motif or in the catalytic glutamate residue are defective in piliation and natural transformation. These findings show that both, ATP binding and hydrolysis, are essential for the dual function of PilF in natural transformation and pilus assembly.
B. Duclos - One of the best experts on this subject based on the ideXlab platform.
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On the binding of ATP to the autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii.
FEBS Letters, 1999Co-Authors: P. Doublet, C. Vincent, C. Grangeasse, Aj Cozzone, B. DuclosAbstract:The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5′-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.
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On the binding of ATP to the autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii.
FEBS Letters, 1999Co-Authors: P. Doublet, C. Vincent, C. Grangeasse, Aj Cozzone, B. DuclosAbstract:The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5'-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii was overproduced, purified to homogeneity and assayed for ATP binding by using the nucleotide analog 5'-p-fluorosulfonylbenzoyl adenosine. The ATP binding site of this bacterial autophosphorylating protein was found to be different from that generally used by eukaryotic protein kinases. It consists of two amino acid sequences that closely resemble the Walker Motifs A and B. This observation was confirmed by site-directed mutagenesis experiments which showed, in addition, that the ATP molecule bound to these Motifs is effectively employed by the bacterial protein to autophosphorylate on tyrosine. It is concluded that even though the overall autophosphorylation reaction is similar in eukaryotic and prokaryotic proteins, the mechanism involved is likely different.
