Networks and clusters of intramolecular interactions, as well as their "communication" across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site) should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme.

Papaleo, E., Pasi, M., Tiberti, M., DE GIOIA, L. (2011). Molecular dynamics of Mesophilic-Like mutants of a Cold-Adapted enzyme: Insights into distal effects induced by the mutations. PLOS ONE, 6(9) [10.1371/journal.pone.0024214].

Molecular dynamics of Mesophilic-Like mutants of a Cold-Adapted enzyme: Insights into distal effects induced by the mutations

PAPALEO, ELENA
;
PASI, MARCO
Secondo
;
TIBERTI, MATTEO
Penultimo
;
DE GIOIA, LUCA
Ultimo
2011

Abstract

Networks and clusters of intramolecular interactions, as well as their "communication" across the three-dimensional architecture have a prominent role in determining protein stability and function. Special attention has been dedicated to their role in thermal adaptation. In the present contribution, seven previously experimentally characterized mutants of a cold-adapted α-amylase, featuring mesophilic-like behavior, have been investigated by multiple molecular dynamics simulations, essential dynamics and analyses of correlated motions and electrostatic interactions. Our data elucidate the molecular mechanisms underlying the ability of single and multiple mutations to globally modulate dynamic properties of the cold-adapted α-amylase, including both local and complex unpredictable distal effects. Our investigation also shows, in agreement with the experimental data, that the conversion of the cold-adapted enzyme in a warm-adapted variant cannot be completely achieved by the introduction of few mutations, also providing the rationale behind these effects. Moreover, pivotal residues, which are likely to mediate the effects induced by the mutations, have been identified from our analyses, as well as a group of suitable candidates for protein engineering. In fact, a subset of residues here identified (as an isoleucine, or networks of mesophilic-like salt bridges in the proximity of the catalytic site) should be considered, in experimental studies, to get a more efficient modification of the features of the cold-adapted enzyme.
Articolo in rivista - Articolo scientifico
Mutagenesis, Site-Directed; Mutation; Protein Structure, Secondary; alpha-Amylases; Molecular Dynamics Simulation; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
English
Papaleo, E., Pasi, M., Tiberti, M., DE GIOIA, L. (2011). Molecular dynamics of Mesophilic-Like mutants of a Cold-Adapted enzyme: Insights into distal effects induced by the mutations. PLOS ONE, 6(9) [10.1371/journal.pone.0024214].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/66371
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