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| rdf:type
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| rdfs:seeAlso
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| Description
| - The accumulation of amyloid- (A) peptide is thought to be a major causative mechanism of Alzheimer's disease. A accumulation could be caused by dysregulated processing of amyloid precursor protein, yielding excessive amounts of A, and/or by inefficient proteolytic degradation of the peptide itself. Several proteases have been described as A degradation enzymes, most notably metalloendopeptidases, aspartic endopeptidases, and some exopeptidases. Recently a report suggested that another metallopeptidase, glutamate carboxypeptidase II (GCPII), can also cleave A. GCPII is a zinc exopeptidase that cleaves glutamate from N-acetyl-l-aspartyl-l-glutamate in the central nervous system and from pteroylpoly--glutamate in the jejunum. GCPII has been proposed as a promising therapeutic target for disorders caused by glutamate neurotoxicity. However, an A-degrading activity of GCPII would compromise potential pharmaceutical use of GCPII inhibitors, because the enzyme inhibition might lead to increased A levels and consequently to Alzheimer's disease. Therefore, we analyzed the reported A-degrading activity of GCPII using highly purified recombinant enzyme and synthetic A. We did not detect any A degradation activity of GCPII or its homologue even under prolonged incubation at a high enzyme to substrate ratio. These results are in good agreement with the current detailed structural understanding of the substrate specificity and enzyme-ligand interactions of GCPII.Sedlak, F., Sacha, P., Blechova, M., Bezinova, A., Safaik, M., Sebestik, J., Konvalinka, J. Glutamate carboxypeptidase II does not process amyloid- peptide.
- The accumulation of amyloid- (A) peptide is thought to be a major causative mechanism of Alzheimer's disease. A accumulation could be caused by dysregulated processing of amyloid precursor protein, yielding excessive amounts of A, and/or by inefficient proteolytic degradation of the peptide itself. Several proteases have been described as A degradation enzymes, most notably metalloendopeptidases, aspartic endopeptidases, and some exopeptidases. Recently a report suggested that another metallopeptidase, glutamate carboxypeptidase II (GCPII), can also cleave A. GCPII is a zinc exopeptidase that cleaves glutamate from N-acetyl-l-aspartyl-l-glutamate in the central nervous system and from pteroylpoly--glutamate in the jejunum. GCPII has been proposed as a promising therapeutic target for disorders caused by glutamate neurotoxicity. However, an A-degrading activity of GCPII would compromise potential pharmaceutical use of GCPII inhibitors, because the enzyme inhibition might lead to increased A levels and consequently to Alzheimer's disease. Therefore, we analyzed the reported A-degrading activity of GCPII using highly purified recombinant enzyme and synthetic A. We did not detect any A degradation activity of GCPII or its homologue even under prolonged incubation at a high enzyme to substrate ratio. These results are in good agreement with the current detailed structural understanding of the substrate specificity and enzyme-ligand interactions of GCPII.Sedlak, F., Sacha, P., Blechova, M., Bezinova, A., Safaik, M., Sebestik, J., Konvalinka, J. Glutamate carboxypeptidase II does not process amyloid- peptide. (en)
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| Title
| - Glutamate carboxypeptidase II does not process amyloid-beta peptide
- Glutamate carboxypeptidase II does not process amyloid-beta peptide (en)
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| skos:prefLabel
| - Glutamate carboxypeptidase II does not process amyloid-beta peptide
- Glutamate carboxypeptidase II does not process amyloid-beta peptide (en)
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| skos:notation
| - RIV/00216208:11310/13:10189921!RIV14-MSM-11310___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00216208:11310/13:10189921
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - depsipeptide; substrate specificity; exopeptidase; disaggregation; Alzheimer's disease; PSMA (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Blechová, Miroslava
- Konvalinka, Jan
- Šebestík, Jaroslav
- Šácha, Pavel
- Šafařík, Martin
- Březinová, Anna
- Sedlák, František
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
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| http://bibframe.org/vocab/doi
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| http://localhost/t...ganizacniJednotka
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