http://www.cnr.it/ontology/cnr/individuo/prodotto/ID4049

Anthrax Lethal Factor Investigated by Molecular Simulations (Articolo in rivista)

Type

Label

Anthrax Lethal Factor Investigated by Molecular Simulations (Articolo in rivista) (literal)

Anno

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

Alternative label

Hong, R; Magistrato, A; Carloni, P (2008)
Anthrax Lethal Factor Investigated by Molecular Simulations
in Journal of chemical theory and computation
(literal)

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Pagina inizio

Pagina fine

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Rivista

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Note

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

[1] SISSA, ISAS, [2] CNR, INFM,Democritos Natl Simulat Ctr, I-34014 Trieste, Italy; [3] IIT, Trieste, Italy (literal)

Titolo

Abstract

\"The anthrax disease is caused by the lethal toxin secreted by the bacterium Bacillus anthracis. The toxin is a protein aggregate which contains a Zn-based hydrolase called anthrax Lethal Factor (LF). In this work, we investigate the structure of its Michaelis complex with an optimized MAPKK-like substrate using several computational methods including density functional theory, molecular dynamics, and coarse grained techniques. Our calculations suggest that (i) the presence of second-shell ligands is crucial for tuning the structure, energetics, and protonation state of the metal binding site, as found in other Zn-based enzymes; (ii) the nucleophilic agent is a Zn-bound water molecule; (iii) substrate binding to the active site groove is mainly stabilized by van der Waals interactions; (iv) the bonds most likely involved in the substrate hydrolysis are only mildly polarized by the protein scaffold; and (v) part of helix alpha 19, which is present in one solid state structure of LF (PDB: 1JKY), assumes a coiled conformation.\" (literal)

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