Accession Number:

ADA279346

Title:

Presynaptic Neurotoxins: Biochemistry, Molecular Biology, Immunology and Other Exploratory Studies

Descriptive Note:

Midterm rept. 1 Sep 1992-1 Mar 1994

Corporate Author:

WYOMING UNIV LARAMIE DEPT OF MOLECULAR BIOLOGY

Personal Author(s):

Report Date:

1994-04-01

Pagination or Media Count:

33.0

Abstract:

We are using multiple approaches employing the tools of biochemistry, immunology, molecular biology, and pharmacology to gain greater insight into presynaptic neurotoxin structure and function. Protein sequencing of phospholipases A2 PLA2 have enabled us to identify suspected residues of presynaptic neurotoxins that are involved in activities such as neurotoxicity, myotoxicity, dimerization, etc., and nucleic acid sequencing of both cDNAs and genomic DNA have provided us with a better understanding of the genomic structure and possible regulatory elements within these genes. Chemical modifications of presynaptic neurotoxins have suggested whether these or similar modifications may be involved in modifying PLA2 function in vivo. Higher-ordered structural analysis of Mojave toxin using the techniques of NMR and x-ray diffraction should complement our protein sequencing studies and allow predictions about other critical amino acid residues. We can now express both subunits of Mojave toxin in E. coli and are working to isolate these products in biologically active forms. Once accomplished, we can conduct site-specific mutagenesis studies coupled with expression to confirm that certain residues are involved in specific functions. Pharmacological experiments have suggested that PLA2 neurotoxins do not appear to be endocytosed to exert their effects, unlike most potent enzymatic toxins. Presynaptic neurotoxins, Protein toxins, Physiologically active compounds, Naturally-occurring toxin inhibitors, RAD IV.

Subject Categories:

  • Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE