Engineering Diptheria Toxin towards the Development of Therapeutics against Breast Cancer

Abstract

We have completed the crystal structure determination of diphtheria toxin bound to its normal receptor (Louie et al., Molecular Cell, 1, 67-78, 1997). The crystal structure of diphtheria toxin (DT) complexed 1:1 with a extracellular fragment of its cell-surface receptor. The toxin receptor is a membrane-bound precursor of a heparin-binding EGF-like growth factor (HB-EGF). The structure reveals that a sheet in the receptor-binding domain of DT packs against a (beta)-sheet of the EGF-like fold. Using a three-dimensional picture as a guide, we have identified key atoms dictating the fit between toxin and receptor and remodify the toxin to target to heregulin, whose overexpression is correlated with the onset of metastatic breast cancer. Future studies will include testing the function of this recombinant toxin in cell culture systems of breast cancer cell lines.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1999
Accession Number
ADA386220

Entities

People

  • Senyon Choe

Organizations

  • Salk Institute for Biological Studies

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Animals
  • Biomedical Research
  • Breast Cancer
  • Chemical Compounds
  • Classification
  • Deoxyribonucleic Acids
  • Electronic Mail
  • Engineering
  • Federal Law
  • Information Operations
  • Laboratory Animals
  • Materials
  • Molecules
  • Neoplasms
  • Recombinant Dna
  • Therapy

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry