Accession Number : ADA338950

Title :   Engineering Diptheria Toxin Towards the Development of Therapeutics Against Breast Cancer

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA

Personal Author(s) : Choe, Senyon

PDF Url : ADA338950

Report Date : SEP 1997

Pagination or Media Count : 12

Abstract : We have completed the crystal structure determination of diphtheria toxin bound to its normal receptor. The crystal structure of diphtheria toxin (DT) complexed 1:1 with a extracellular fragment of its cell-surface receptor reveals that a Beta-sheet in the receptor-binding domain of DT packs against a Beta-sheet of the EGF-like fold of the receptor, thus the interaction is primarily mediated through side chains. Such unusual interaction as the protein-protein interface provides an excellent structural basis for altering side chains to modulate the binding specificity of the toxin to other EGF-like receptors. Using a three-dimensional picture as a guide, we have identified key atoms dictating the fit between toxin and receptor. To fit to the new molecular surface provided by heregulin that is distinct from that of the natural toxin receptor, we will modify amino acids of the toxin surrounding heregulin-specific amino acids by molecular biology techniques.

Descriptors :   *BACTERIAL TOXINS, *CORYNEBACTERIUM DIPHTHERIAE, *BREAST CANCER, EPITHELIUM, CRYSTAL STRUCTURE, PROTEINS, THERAPY, MOLECULAR BIOLOGY, CELLS(BIOLOGY), CULTURES(BIOLOGY), TOXINS AND ANTITOXINS, RECEPTOR SITES(PHYSIOLOGY), AMINO ACIDS, MUCOUS MEMBRANES, EUBACTERIALES.

Subject Categories : Medicine and Medical Research
      Toxicology
      Microbiology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE