Structural determinants of the high thermal stability of SsoPox from the hyperthermophilic archaeon Sulfolobus solfataricus

Vecchio, Pompea Del; Elias, Mikael; Merone, Luigia; Graziano, Giuseppe; Dupuy, Jérôme; Mandrich, Luigi; Carullo, Paola; Fournier, Bertrand; Rochu, Daniel; Rossi, Mosè; Masson, Patrick; Chabrière, Éric; Manco, Giuseppe

doi:10.1007/s00792-009-0231-9

Cited by 58 publications

(58 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its structure was determined in the free form and also in complex with an HSL analog (45,46). The active site of SsoPox shows striking resemblance to that of AiiA (Fig.…”

Section: Phosphotriesterase-like Lactonasesmentioning

confidence: 99%

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Elias

Tawfik

2012

Journal of Biological Chemistry

Self Cite

115

141

View full text Add to dashboard Cite

We discuss the basic features of divergent versus convergent evolution and of the common scenario of parallel evolution. The example of quorum-quenching lactonases is subsequently described. Three different quorum-quenching lactonase families are known, and they belong to three different superfamilies. Their key active-site architectures have converged and are strikingly similar. Curiously, a promiscuous organophosphate hydrolase activity is observed in all three families. We describe the structural and mechanistic features that underline this converged promiscuity and how this promiscuity drove the parallel divergence of organophosphate hydrolases within these lactonase families by either natural or laboratory evolution.

show abstract

“…Its structure was determined in the free form and also in complex with an HSL analog (45,46). The active site of SsoPox shows striking resemblance to that of AiiA (Fig.…”

Section: Phosphotriesterase-like Lactonasesmentioning

confidence: 99%

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Elias

Tawfik

2012

Journal of Biological Chemistry

Self Cite

115

141

View full text Add to dashboard Cite

show abstract

“…Thermostable PTEs from thermophilic bacteria (Merone et al, 2005; Elias et al, 2008; Del Vecchio et al, 2009) or mutated/evolved highly stable enzymes from mesophilic bacteria are promising for topical protection and decontamination. PTE was also entrapped in additives for latex coating of biodefensive surfaces.…”

Section: 2 Potential Enzymesmentioning

confidence: 99%

Catalytic Bioscavengers Against Toxic Esters, an Alternative Approach for Prophylaxis and Treatments of Poisonings

Masson¹,

Rochu²

2009

Acta Naturae

View full text Add to dashboard Cite

Bioscavengers are biopharmaceuticals that specifically react with toxicants. Thus, enzymes reacting with poisonous esters can be used as bioscavengers for neutralization of toxic molecules before they reach physiological targets. Parenteral administration of bioscavengers is, therefore, intended for prophylaxis or pre-treatments, emergency and post-exposure treatments of intoxications. These enzymes can also be used for application on skin, mucosa and wounds as active components of topical skin protectants and decontamination solutions. Human butyrylcholinesterase is the first stoichiometric bioscavenger for safe and efficient prophylaxis of organophosphate poisoning. However, huge amounts of a costly enzyme are needed for protection. Thus, the bioscavenger approach will be greatly improved by the use of catalytic bioscavengers. Catalytic bioscavengers are enzymes capable of degrading toxic esters with a turnover. Suitable catalytic bioscavengers are engineered mutants of human enzymes. Efficient mutants of human butyrylcholinesterase have been made that hydrolyze cocaine at a high rate. Mutants of human cholinesterases capable of hydrolyzing OPs have been made, but so far their activity is too low to be of medical interest. Human paraoxonase a promiscuous plasma enzyme is certainly the most promising phosphotriesterase. However, its biotechnology is still in its infancy. Other enzymes and proteins from blood and organs, and secondary biological targets of OPs and carbamates are potential bioscavengers, in particular serum albumin that reacts with OPs and self-reactivates. Lastly, non-human enzymes, phosphotriesterases and oxidases from various bacterial and eukaryotic sources could be used for external use against OP poisoning and for internal use after modifications for immunological compatibility.

show abstract

“…PTEs and PLLs, which belong to the amidohydrolase superfamily (Seibert & Raushel, 2005), share the same (/) 8 topology in which a bimetallic centre is coordinated by four histidines, an aspartic acid and a carboxylated lysine (Elias et al, 2008;Del Vecchio et al, 2009). The bimetallic centre activates a water molecule into a hydroxide ion, which serves as a nucleophile for the hydrolysis of OPs or AHLs.…”

Section: Introductionmentioning

confidence: 99%

Crystallization and preliminary X-ray diffraction analysis of the lactonaseVmoLac fromVulcanisaeta moutnovskia

et al. 2013

Self Cite

View full text Add to dashboard Cite

Phosphotriesterase-like lactonases (PLLs) are native lactonases that are capable of hydrolyzing lactones such as aliphatic lactones or acyl-homoserine lactones, which are involved in bacterial quorum sensing. Previously characterized PLLs are moreover endowed with a promiscuous phosphotriesterase activity and are therefore able to detoxify organophosphate insecticides. A novel PLL representative, dubbed VmoLac, has been identified from the hyperthermophilic crenarchaeon Vulcanisaeta moutnovskia. Because of its intrinsic high thermal stability, VmoLac may constitute an appealing candidate for engineering studies with the aim of producing an efficient biodecontaminant for organophosphorus compounds and a bacterial antivirulence agent. In combination with biochemical studies, structural information will allow the identification of the residues involved in substrate specificity and an understanding of the enzymatic catalytic mechanisms. Here, the expression, purification, crystallization and X-ray data collection at 2.4 Å resolution of VmoLac are reported.

show abstract

Structural determinants of the high thermal stability of SsoPox from the hyperthermophilic archaeon Sulfolobus solfataricus

Cited by 58 publications

References 55 publications

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Catalytic Bioscavengers Against Toxic Esters, an Alternative Approach for Prophylaxis and Treatments of Poisonings

Crystallization and preliminary X-ray diffraction analysis of the lactonaseVmoLac fromVulcanisaeta moutnovskia

Contact Info

Product

Resources

About