The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors
In the present work, we studied the inhibitory and kinetic implications of classical PTP1B inhibitors (chlorogenic acid, ursolic acid, suramin) using three enzyme constructs (hPTP1B1-285, hPTP1B1-321, and hPTP1B1-400). The results indicate that the unstructured region of PTP1B (300-400 amino acids)...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2170369 |
| _version_ | 1827123374109753344 |
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| author | Andrea Coronell-Tovar Francisco Cortés-Benítez Martin González-Andrade |
| author_facet | Andrea Coronell-Tovar Francisco Cortés-Benítez Martin González-Andrade |
| author_sort | Andrea Coronell-Tovar |
| collection | DOAJ |
| description | In the present work, we studied the inhibitory and kinetic implications of classical PTP1B inhibitors (chlorogenic acid, ursolic acid, suramin) using three enzyme constructs (hPTP1B1-285, hPTP1B1-321, and hPTP1B1-400). The results indicate that the unstructured region of PTP1B (300-400 amino acids) is very important both to obtain optimal inhibitory results and propose classical inhibition mechanisms (competitive or non-competitive) through kinetic studies. The IC50 calculated for ursolic acid and suramin using hPTP1B1-400 are around four and three times lower to the short form of the enzyme, the complete form of PTP1B, the one found in the cytosol (in vivo). On the other hand, we highlight the studies of enzymatic kinetics using the hPTP1B1-400 to know the type of enzymatic inhibition and to be able to direct docking studies, where the unstructured region of the enzyme can be one more option for binding compounds with inhibitory activity. |
| first_indexed | 2024-03-09T02:03:15Z |
| format | Article |
| id | doaj.art-d9b22f6f1731457b9a605dbd036f1d1b |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:54Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-d9b22f6f1731457b9a605dbd036f1d1b2024-09-09T17:23:18ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2170369The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitorsAndrea Coronell-Tovar0Francisco Cortés-Benítez1Martin González-Andrade2Departamento de Bioquímica, Facultad de Medicina, Laboratorio de Biosensores y Modelaje molecular, Universidad Nacional Autónoma de México, Ciudad de México, MéxicoDepartamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México, MéxicoDepartamento de Bioquímica, Facultad de Medicina, Laboratorio de Biosensores y Modelaje molecular, Universidad Nacional Autónoma de México, Ciudad de México, MéxicoIn the present work, we studied the inhibitory and kinetic implications of classical PTP1B inhibitors (chlorogenic acid, ursolic acid, suramin) using three enzyme constructs (hPTP1B1-285, hPTP1B1-321, and hPTP1B1-400). The results indicate that the unstructured region of PTP1B (300-400 amino acids) is very important both to obtain optimal inhibitory results and propose classical inhibition mechanisms (competitive or non-competitive) through kinetic studies. The IC50 calculated for ursolic acid and suramin using hPTP1B1-400 are around four and three times lower to the short form of the enzyme, the complete form of PTP1B, the one found in the cytosol (in vivo). On the other hand, we highlight the studies of enzymatic kinetics using the hPTP1B1-400 to know the type of enzymatic inhibition and to be able to direct docking studies, where the unstructured region of the enzyme can be one more option for binding compounds with inhibitory activity.https://www.tandfonline.com/doi/10.1080/14756366.2023.2170369Diabetes mellitus PTP1B1-400kinetic assayinhibidors PTP1Bdocking PTP1B |
| spellingShingle | Andrea Coronell-Tovar Francisco Cortés-Benítez Martin González-Andrade The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Diabetes mellitus PTP1B1-400 kinetic assay inhibidors PTP1B docking PTP1B |
| title | The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors |
| title_full | The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors |
| title_fullStr | The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors |
| title_full_unstemmed | The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors |
| title_short | The importance of including the C-terminal domain of PTP1B1-400 to identify potential antidiabetic inhibitors |
| title_sort | importance of including the c terminal domain of ptp1b1 400 to identify potential antidiabetic inhibitors |
| topic | Diabetes mellitus PTP1B1-400 kinetic assay inhibidors PTP1B docking PTP1B |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2170369 |
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