Work

Site‐directed mutagenesis of K396R of the 65 kDa glutamic acid decarboxylase active site obliterates enzyme activity but not antibody binding

Year: 2001

Type: article

Abstract: The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutamate decarboxylase (GAD65) was analyzed using the K396R GAD65 mutant. GAD65 is a major autoantigen in Type 1 diabetes and autoantibodies directed to GAD65 are widely used markers for this disease. We found that (1) recombinant human GAD65 is fully enzymatically active; (2) the K396R mutation abolished GAD65 activity; and (3) the K396R mutant retained full antigenicity to GAD65 autoantibodies in serum from Type 1 diabetes patients, but not to polyclonal antibodies raised to the catalytic domain.

Source: FEBS Letters

DOI: 10.1016/s0014-5793(00)02429-7

Authors: Christiane S. Hampe, Lisa P. Hammerle, Alberto Falorni, John Robertson, Åke Lernmark

Institutions: University of Washington, University of Perugia, Karolinska University Hospital, Mertiva (Sweden)

Language: English

Topic: Diabetes and associated disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases