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| Item Type: | Article |
|---|---|
| Title: | Domain specific characteristics of the bifunctional key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase |
| Creators Name: | Blume, A., Weidemann, W., Stelzl, U., Wanker, E.E., Lucka, L., Donner, P., Reutter, W., Horstkorte, R. and Hinderlich, S. |
| Abstract: | UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is a bifunctional enzyme, which initiates and regulates sialic acid biosynthesis. Sialic acids are important compounds of mammalian glycoconjugates, mediating several biological processes, such as cell-cell or cell-matrix interactions. In order to characterize the function of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, a number of deletion mutants were generated, lacking either parts of the N-terminal epimerase or the C-terminal kinase domain. N-terminal deletion of only 39 amino acids results in a complete loss of epimerase activity. Deletions in the C-terminal part result in a reduction or complete loss of kinase activity, depending on the size of the deletion. Deletions at either the N- or the C-terminus also result in a reduction of the other enzyme activity. These results indicate that a separate expression of both domains is possible, but that a strong intramolecular dependency of the two domains has arisen during evolution of the enzyme. N-terminal, as well as C-terminal, mutants tend to form trimers, in addition to the hexameric structure of the native enzyme. These results and yeast two-hybrid experiments show that structures required for dimerization are localized within the kinase domain, and a potential trimerization site is possibly located in a region between the two domains. In conclusion, our results reveal that the activities, as well as the oligomeric structure, of this bifunctional enzyme seem to be organized and regulated in a complex manner. |
| Keywords: | Deletion Mutant, Domain, Sialic Acid, UDP-N-Acetylglucosamine 2-Epimerase, Yeast Two-Hybrid Assay, Animals, Rats |
| Source: | Biochemical Journal |
| ISSN: | 0264-6021 |
| Publisher: | Portland Press |
| Volume: | 384 |
| Number: | 3 |
| Page Range: | 599-607 |
| Date: | 26 August 2004 |
| Official Publication: | https://doi.org/10.1042/BJ20040917 |
| PubMed: | View item in PubMed |
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