Accession Number : ADA313591

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

Descriptive Note : Final rept. 1 Sep 92-31 May 96,

Corporate Author : WYOMING UNIV LARAMIE

Personal Author(s) : Kaiser, Ivan I.

PDF Url : ADA313591

Report Date : JUN 1996

Pagination or Media Count : 88

Abstract : Multiple approaches employing the tools of biochemistry, immunology, molecular biology, microscopy, and pharmacology have been used to gain greater insight into phospholipase A2 (PLA2) structure, function, and solution properties. Protein sequencing has enabled us to identify suspected residues and molecular domains of PLA2s, expressing neurotoxicity, myotoxicity, hemorrhage, hypotension, and dimerization; and DNA sequencing of both cDNAs and genomic DNA has provided us with a better understanding of genomic structure, possible regulatory elements within these genes, and insights into PLA2 gene evolution. Chemical modifications have suggested whether alterations may be involved in modifying PLA2 function in vivo, and whether subunit dissociation is essential for function. NMR and x-ray diffraction have been initiated and should eventually allow predictions about other critical' residues. We expressed both subunits of Mojave toxin in E. coli, and procedures need to be developed to recover these products in biologically active forms. Once accomplished, site-specific mutagenesis studies coupled with expression to confirm that certain residues are involved in specific functions can be conducted. Pharmacological experiments have suggested that PLA2 neurotoxins do not appear to be endocytosed to exert their effects, unlike most potent enzymatic toxins. Endogenous sera and venom toxin inhibitors have been identified and partially characterized.

Descriptors :   *BIOCHEMISTRY, *NERVOUS SYSTEM, *MOLECULAR BIOLOGY, *IMMUNOLOGY, *PHARMACOLOGY, *NEUROTOXINS, FUNCTIONS, NUCLEAR MAGNETIC RESONANCE, TOOLS, TOXICITY, ENZYMES, PROTEINS, X RAY DIFFRACTION, DEOXYRIBONUCLEIC ACIDS, ESCHERICHIA COLI, SOLUTIONS(GENERAL), GENES, INHIBITORS, DISSOCIATION, VENOMS, POTENCY, TOXINS AND ANTITOXINS, DIMERS, HEMORRHAGE, HYPOTENSION.

Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE