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Computational insights into the interaction of the anthrax lethal factor with the N-terminal region of its substrates by Manali Joshi; Jerry Osagie Ebalunode; James M. Briggs is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract The anthrax lethal factor is a zinc metalloprotease toxin secreted by __Bacillus anthracis__ which cleaves at the N‐terminal region of six mitogen activated protein kinase kinases (MEKs) in the cell. Additionally, it is known to cleave a nine residue peptide “LF10,” 50‐fold more efficiently than nine residues of MEK1. There is very little sequence similarity between the MEK N‐termini, thus, it is unclear how the lethal factor can accommodate and cleave the diverse N‐termini of the MEKs and whether there is a hierarchy in this interaction, as there is between LF10 and MEK1. To investigate this problem, we carried out multiple molecular dynamics simulations of the lethal factor with nine residues of each of the substrates. Our simulations reveal that like LF10, certain MEK substrates have residue compositions that favor β‐sheet formation with the lethal factor over others. The formation of this secondary structure maintains a catalytic conformation. Binding energetics using the MM‐PBSA method was used to rank‐order the substrates for their affinity to LF (__K__~M~). On the basis of the results, we conclude that the LF does not equally accommodate the MEK substrates and fu

Who reads Computational insights into the interaction of the anthrax lethal factor with the N-terminal region of its substrates?

Author

Manali Joshi; Jerry Osagie Ebalunode; James M. Briggs

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)

Published

2008

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)