Skip NavigationSkip to Content
Return Return to Search Results

Involvement of domain II in toxicity of anthrax lethal factor

  1. Author:
    Liang, X. D.
    Young, J. J.
    Boone, S. A.
    Waugh, D. S.
    Duesbery, N. S.

  2. Author Address

    Van Andel Res Inst, Lab Canc & Dev Cell Biol, Grand Rapids, MI 49503 USA. NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA Duesbery, NS, Van Andel Res Inst, Lab Canc & Dev Cell Biol, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA
    1. Year: 2004
    2. Date: DEC 10
  2. Journal: Journal of Biological Chemistry
    1. 279
    2. 50
    3. Pages: 52473-52478
  4. Type of Article: Article
  1. Abstract:

    Anthrax lethal factor (LF) is a Zn2+-metalloprotease that cleaves and inactivates mitogen-activated protein kinase kinases (MEKs). We have used site-directed mutagenesis to identify a cluster of residues in domain II of LF that lie outside the active site and are required for cellular proteolytic activity toward MEKs. Alanine substituted for Leu(293), Lys(294), Leu(514), Asn(516), or Arg(491) caused a 10-50-fold reduction in LF toxicity. Further, whereas pairwise substitution of alanine for Leu(514) and either Leu(293), Lys(294), or Arg(491) completely abrogated LF toxicity, pairwise mutation of Leu(514) and Asn(516) resulted in toxicity comparable with N516A alone. The introduction of these mutations reduced LF-mediated cleavage of MEK2 in cell-based assays but altered neither the ability of LF to bind protective antigen nor its ability to translocate across a membrane. Interestingly, direct in vitro measurement of LF activity indicated that decreased toxicity was not always accompanied by reduced proteolytic activity. However, mutations in this region significantly reduced the ability of LF to competitively inhibit B-Raf phosphorylation of MEK. These results provide evidence that elements of domain II are involved in the association of LF into productive complex with MEKs

    See More

  1. Keywords:

External Sources

  1. View record in Web of Science®
  2. WOS: 000225493400092

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel