Skip NavigationSkip to Content
Return Return to Search Results

Cysteine 81 Is Critical for the Interaction of S100A4 and Myosin-IIA

  1. Author:
    Dulyaninova, N. G.
    Hite, K. M.
    Zencheck, W. D.
    Scudiero, D. A.
    Almo, S. C.
    Shoemaker, R. H.
    Bresnick, A. R.

  2. Author Address

    [Dulyaninova, NG; Zencheck, WD; Almo, SC; Bresnick, AR] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. [Hite, KM; Scudiero, DA] Natl Canc Inst Frederick, SAIC Frederick, Frederick, MD 21702 USA. [Shoemaker, RH] Natl Canc Inst Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Natl Inst Hlth, Frederick, MD 21702 USA.;Bresnick, AR (reprint author), Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA;anne.bresnick@einstein.yu.edu
    1. Year: 2011
    2. Date: Aug
  2. Journal: Biochemistry
    1. 50
    2. 33
    3. Pages: 7218-7227
  4. Type of Article: Article
  5. ISSN: 0006-2960
  1. Abstract:

    Overexpression of S100A4, a member of the S100 family of Ca(2+)-binding proteins, is associated with a number of human pathologies, including fibrosis, inflammatory disorders, and metastatic disease. The identification of small molecules that disrupt S100A4/target interactions provides a mechanism for inhibiting S100A4-mediated cellular activities and their associated pathologies. Using an anisotropy assay that monitors the Ca(2+)-dependent binding of myosin-IIA to S100A4, NSC 95397 was identified as an inhibitor that disrupts the S100A4/myosin-IIA interaction and inhibits S100A4-mediated depolymerization of myosin-ILA filaments. Mass spectrometry demonstrated that NSC 95397 forms covalent adducts with Cys81 and Cys86, which are located in the canonical target binding cleft. Mutagenesis studies showed that covalent modification of just Cys81 is sufficient to inhibit S100A4 function with respect to myosin-IIA binding and depolymerization. Remarkably, substitution of Cys81 with serine or alanine significantly impaired the ability of S100A4 to promote myosin-IIA filament disassembly. As reversible covalent cysteine modifications have been observed for several S100 proteins, we propose that modification of Cys81 may provide an additional regulatory mechanism for mediating the binding of S100A4 to myosin-IIA.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1021/bi200853y
  3. View record in Web of Science®
  4. WOS: 000294076100015

Library Notes

  1. Fiscal Year: FY2010-2011
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