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 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.
Lush
M J
MJ
MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK.
Li
Y
Y
Read
D J
DJ
Willis
A C
AC
Glynn
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000473:pathology; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics*; D009943:Organophosphorus Compounds / Q000378:metabolism; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry*
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009943:Organophosphorus Compounds; C108350:SWS protein, Drosophila; C088489:1-(saligenin cyclic phospho)-9-biotinyldiaminononane; D001710:Biotin; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D012697:Serine Endopeptidases