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Structure and function of the presynaptically neurotoxic phospholipase A² from the Australian tiger snake - Notechis scutatus scutatus
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry.
1997 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Notexin is a member of the phospholipase A2, (PLA2) family of proteins. Despitethe fact they are homologous proteins with similar sequence and almost identicalstructures, they show an impressing diversity of functions. Notexin is a potentneurotoxin and as a first step in elucidating the basis for its neurotoxicity, thethree-dimensional structure was solved. The structure was similar to otherknown PLA2s, but revealed two or three binding-sites for quartenary-ions, givingnotexin an alternative and unique conformation in one part of the molecule. Toget an idea of the binding site of notexin for its target, notexin was immobilisedon an agarose matrix using a spacer which binds specifically to the active site.Immobilised in this way, the opening to the catalytic site faces inward.Synaptosomes (nerve-endings) chromatographed on this matrix were indeedretarded. They could not be desorbed by changing the ion-strength or pH but weredesorbed upon addition of ligand (notexin). This implies a specific bindingexerted by a structure on notexin removed from the opening of the catalytic site.To be able to study the function of notexin in more detail, a recombinant proteinwas made by expressing a synthetic gene in E. coli. The structures of ananticoagulant and another neurotoxic PLA2 were also compared.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1997. , 48 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 299
Keyword [en]
Keyword [sv]
National Category
Biochemistry and Molecular Biology
Research subject
URN: urn:nbn:se:uu:diva-843ISBN: 91-554-4012-6OAI: oai:DiVA.org:uu-843DiVA: diva2:171375
Public defence
1997-09-26, lecture hall 822, Uppsala, Biomedical Centre (BMC), Uppsala, 10:00
Available from: 1997-09-05 Created: 1997-09-05Bibliographically approved

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