Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down
Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialyla...
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/17/5203 |
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| author | Ravneet Kaur Grewal Abdul Rajjak Shaikh Suresh Gorle Manjeet Kaur Paula Alexendra Videira Luigi Cavallo Mohit Chawla |
| author_facet | Ravneet Kaur Grewal Abdul Rajjak Shaikh Suresh Gorle Manjeet Kaur Paula Alexendra Videira Luigi Cavallo Mohit Chawla |
| author_sort | Ravneet Kaur Grewal |
| collection | DOAJ |
| description | Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer. |
| first_indexed | 2024-03-10T08:07:01Z |
| format | Article |
| id | doaj.art-927080da83bc4c249ebb7ec2537c5536 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:07:01Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-927080da83bc4c249ebb7ec2537c55362023-11-22T11:00:44ZengMDPI AGMolecules1420-30492021-08-012617520310.3390/molecules26175203Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way DownRavneet Kaur Grewal0Abdul Rajjak Shaikh1Suresh Gorle2Manjeet Kaur3Paula Alexendra Videira4Luigi Cavallo5Mohit Chawla6STEMskills Research and Education Lab Private Limited, Faridabad 121002, Haryana, IndiaSTEMskills Research and Education Lab Private Limited, Faridabad 121002, Haryana, IndiaSTEMskills Research and Education Lab Private Limited, Faridabad 121002, Haryana, IndiaBiotechnology Engineering, University Institute of Engineering & Technology (UIET), Maharshi Dayanand University, Rohtak 124001, Haryana, IndiaAssociate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, PortugalKaust Catalysis Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi ArabiaKaust Catalysis Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi ArabiaMammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.https://www.mdpi.com/1420-3049/26/17/5203sialyltransferasefucosyltransferaseglyocosyltransferases in cancerdrug design |
| spellingShingle | Ravneet Kaur Grewal Abdul Rajjak Shaikh Suresh Gorle Manjeet Kaur Paula Alexendra Videira Luigi Cavallo Mohit Chawla Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down Molecules sialyltransferase fucosyltransferase glyocosyltransferases in cancer drug design |
| title | Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down |
| title_full | Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down |
| title_fullStr | Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down |
| title_full_unstemmed | Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down |
| title_short | Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down |
| title_sort | structural insights in mammalian sialyltransferases and fucosyltransferases we have come a long way but it is still a long way down |
| topic | sialyltransferase fucosyltransferase glyocosyltransferases in cancer drug design |
| url | https://www.mdpi.com/1420-3049/26/17/5203 |
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