{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T16:51:26Z","timestamp":1715964686788},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,9,2]],"date-time":"2008-09-02T00:00:00Z","timestamp":1220313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The anthrax lethal factor is a zinc metalloprotease toxin secreted by <jats:italic>Bacillus anthracis<\/jats:italic> which cleaves at the N\u2010terminal region of six mitogen activated protein kinase kinases (MEKs) in the cell. Additionally, it is known to cleave a nine residue peptide \u201cLF10,\u201d 50\u2010fold more efficiently than nine residues of MEK1. There is very little sequence similarity between the MEK N\u2010termini, thus, it is unclear how the lethal factor can accommodate and cleave the diverse N\u2010termini 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 \u03b2\u2010sheet formation with the lethal factor over others. The formation of this secondary structure maintains a catalytic conformation. Binding energetics using the MM\u2010PBSA method was used to rank\u2010order the substrates for their affinity to LF (<jats:italic>K<\/jats:italic><jats:sub>M<\/jats:sub>). On the basis of the results, we conclude that the LF does not equally accommodate the MEK substrates and further predict that there will be differences between rates of cleavage among the nine residue MEK N\u2010termini. Proteins 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.22241","type":"journal-article","created":{"date-parts":[[2008,9,2]],"date-time":"2008-09-02T15:27:31Z","timestamp":1220369251000},"page":"323-335","source":"Crossref","is-referenced-by-count":10,"title":["Computational insights into the interaction of the anthrax lethal factor with the N\u2010terminal region of its substrates"],"prefix":"10.1002","volume":"75","author":[{"given":"Manali","family":"Joshi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry Osagie","family":"Ebalunode","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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