Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man

The N-terminal amino acid sequences of proteolytic fragments of neuropathy target esterase (NTE), covalently labelled on its active-site serine by a biotinylated organophosphorus ester, were determined and used to deduce the location of this serine residue and to initiate cloning of its cDNA. A puta...

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Bibliographic Details
Published in:Biochemical journal 1998-05, Vol.332 ( Pt 1) (1), p.1-4
Main Authors: Lush, M J, Li, Y, Read, D J, Willis, A C, Glynn, P
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Binding Sites - physiology
Biotin - analogs & derivatives
Biotin - metabolism
Brain - pathology
Carboxylic Ester Hydrolases - chemistry
Cloning, Molecular
Conserved Sequence
Drosophila Proteins
Evolution, Molecular
Humans
Molecular Sequence Data
Mutation - genetics
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - genetics
Neurodegenerative Diseases - genetics
Organophosphorus Compounds - metabolism
Protein Structure, Secondary
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Serine Endopeptidases - chemistry
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Summary:The N-terminal amino acid sequences of proteolytic fragments of neuropathy target esterase (NTE), covalently labelled on its active-site serine by a biotinylated organophosphorus ester, were determined and used to deduce the location of this serine residue and to initiate cloning of its cDNA. A putative NTE clone, isolated from a human foetal brain cDNA library, encoded a 1327 residue polypeptide with no homology to any known serine esterases or proteases. The active-site serine of NTE (Ser-966) lay in the centre of a predicted hydrophobic helix within a 200-amino-acid C-terminal domain with marked similarity to conceptual proteins in bacteria, yeast and nematodes; these proteins may comprise a novel family of potential serine hydrolases. The Swiss Cheese protein which, when mutated, leads to widespread cell death in Drosophila brain [Kretzschmar, Hasan, Sharma, Heisenberg and Benzer (1997) J. Neurosci. 17, 7425-7432], was strikingly homologous to NTE, suggesting that genetically altered NTE may be involved in human neurodegenerative disease.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3320001