Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine
Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis...
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ftmdpi:oai:mdpi.com:/1422-0067/22/8/4079/ 2023-08-20T04:05:47+02:00 Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine Aram Ismail Elizabeth Lewis Birgitta Sjödin Bengt Mannervik agris 2021-04-15 application/pdf https://doi.org/10.3390/ijms22084079 EN eng Multidisciplinary Digital Publishing Institute Biochemistry https://dx.doi.org/10.3390/ijms22084079 https://creativecommons.org/licenses/by/4.0/ International Journal of Molecular Sciences; Volume 22; Issue 8; Pages: 4079 Telcyta veterinary medicine enzyme-activated chemotherapy prodrugs dog GST P1-1 Text 2021 ftmdpi https://doi.org/10.3390/ijms22084079 2023-08-01T01:30:25Z Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis lupus familiaris, has merits as a marker for tumors and as a target for enzyme-activated prodrugs. We produced the canine enzyme CluGST P1-1 by heterologous bacterial expression and verified its cross-reactivity with antihuman-GST P1-1 antibodies. The catalytic activity with alternative substrates of biological significance was determined, and the most active substrate found was benzyl isothiocyanate. Among established GST inhibitors, Cibacron Blue showed positive cooperativity with an IC50 value of 43 nM. Dog GST P1-1 catalyzes activation of the prodrug Telcyta, but the activity is significantly lower than that of the human homolog. Text Canis lupus MDPI Open Access Publishing International Journal of Molecular Sciences 22 8 4079 |
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MDPI Open Access Publishing |
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ftmdpi |
language |
English |
topic |
Telcyta veterinary medicine enzyme-activated chemotherapy prodrugs dog GST P1-1 |
spellingShingle |
Telcyta veterinary medicine enzyme-activated chemotherapy prodrugs dog GST P1-1 Aram Ismail Elizabeth Lewis Birgitta Sjödin Bengt Mannervik Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
topic_facet |
Telcyta veterinary medicine enzyme-activated chemotherapy prodrugs dog GST P1-1 |
description |
Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis lupus familiaris, has merits as a marker for tumors and as a target for enzyme-activated prodrugs. We produced the canine enzyme CluGST P1-1 by heterologous bacterial expression and verified its cross-reactivity with antihuman-GST P1-1 antibodies. The catalytic activity with alternative substrates of biological significance was determined, and the most active substrate found was benzyl isothiocyanate. Among established GST inhibitors, Cibacron Blue showed positive cooperativity with an IC50 value of 43 nM. Dog GST P1-1 catalyzes activation of the prodrug Telcyta, but the activity is significantly lower than that of the human homolog. |
format |
Text |
author |
Aram Ismail Elizabeth Lewis Birgitta Sjödin Bengt Mannervik |
author_facet |
Aram Ismail Elizabeth Lewis Birgitta Sjödin Bengt Mannervik |
author_sort |
Aram Ismail |
title |
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
title_short |
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
title_full |
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
title_fullStr |
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
title_full_unstemmed |
Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine |
title_sort |
characterization of dog glutathione transferase p1-1, an enzyme relevant to veterinary medicine |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2021 |
url |
https://doi.org/10.3390/ijms22084079 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
International Journal of Molecular Sciences; Volume 22; Issue 8; Pages: 4079 |
op_relation |
Biochemistry https://dx.doi.org/10.3390/ijms22084079 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/ijms22084079 |
container_title |
International Journal of Molecular Sciences |
container_volume |
22 |
container_issue |
8 |
container_start_page |
4079 |
_version_ |
1774716512847790080 |