Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine
| Autor: | Aram Ismail, Elizabeth Lewis, Birgitta Sjödin, Bengt Mannervik |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Telcyta enzyme-activated chemotherapy Article Protein Structure Tertiary Substrate Specificity lcsh:Chemistry Dogs veterinary medicine lcsh:Biology (General) lcsh:QD1-999 Glutathione S-Transferase pi prodrugs Biocatalysis Animals Humans dog GST P1-1 Amino Acid Sequence lcsh:QH301-705.5 |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 8 International Journal of Molecular Sciences, Vol 22, Iss 4079, p 4079 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22084079 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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