scholarly journals Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs

2016 ◽  
Vol 7 (6) ◽  
pp. 3928-3933 ◽  
Author(s):  
Olaia Nieto-Garcia ◽  
Paul R. Wratil ◽  
Long D. Nguyen ◽  
Verena Böhrsch ◽  
Stephan Hinderlich ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Acid Biosynthesis ◽  
Key Enzyme ◽  
Potential Inhibitors

Synthetically accessible C6-analogs ofN-acetylmannosamine (ManNAc) were tested as potential inhibitors of the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE/MNK), the key enzyme of sialic acid biosynthesis.

Synthesis of 2-Acetamido-2-Deoxy-D-Mannose Analogues as Potential Inhibitors of Sialic Acid Biosynthesis

1991 ◽  
Vol 10 (2) ◽  
pp. 215-237 ◽  
Author(s):  
H. J. G. Broxterman ◽  
G. A. van der Marel ◽  
J. H. van Boom
Keyword(s):  
Sialic Acid ◽  
Acid Biosynthesis ◽  
Potential Inhibitors

scholarly journals Characterization of Ligand Binding to the Bifunctional Key Enzyme in the Sialic Acid Biosynthesis by NMR

2004 ◽  
Vol 279 (53) ◽  
pp. 55722-55727 ◽  
Author(s):  
Andrew J. Benie ◽  
Astrid Blume ◽  
Richard R. Schmidt ◽  
Werner Reutter ◽  
Stephan Hinderlich ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Ligand Binding ◽  
Acid Biosynthesis ◽  
Key Enzyme

scholarly journals Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Sheng-Chia Chen ◽  
Chi-Hung Huang ◽  
Shu-Jung Lai ◽  
Chia Shin Yang ◽  
Tzu-Hung Hsiao ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Acid Biosynthesis ◽  
Key Enzyme

scholarly journals Domain-specific characteristics of the bifunctional key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

2004 ◽  
Vol 384 (3) ◽  
pp. 599-607 ◽  
Author(s):  
Astrid BLUME ◽  
Wenke WEIDEMANN ◽  
Ulrich STELZL ◽  
Erich E. WANKER ◽  
Lothar LUCKA ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Kinase Domain ◽  
Complete Loss ◽  
Bifunctional Enzyme ◽  
Acid Biosynthesis ◽  
Domain Specific ◽  
Cell Matrix ◽  
C Terminus ◽  
Key Enzyme ◽  
Cell Matrix Interactions

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.

scholarly journals Characterization of Ligand Binding to the Bifunctional Key Enzyme in the Sialic Acid Biosynthesis by NMR

2004 ◽  
Vol 279 (53) ◽  
pp. 55715-55721 ◽  
Author(s):  
Astrid Blume ◽  
Andrew J. Benie ◽  
Florian Stolz ◽  
Richard R. Schmidt ◽  
Werner Reutter ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Ligand Binding ◽  
Acid Biosynthesis ◽  
Key Enzyme

Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis

2009 ◽  
Vol 390 (7) ◽  
Author(s):  
Stefan O. Reinke ◽  
Gerhard Lehmer ◽  
Stephan Hinderlich ◽  
Werner Reutter
Keyword(s):  
Sialic Acid ◽  
Crucial Role ◽  
Feedback Inhibition ◽  
Acid Biosynthesis ◽  
Knock Out ◽  
Acetylneuraminic Acid ◽  
Kinase C ◽  
Key Enzyme ◽  
Hereditary Inclusion Body Myopathy

AbstractThe key enzyme for the biosynthesis ofN-acetylneuraminic acid, from which all other sialic acids are formed, is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). GNE is a highly conserved protein found throughout the animal kingdom. Its highest expression is seen in the liver and placenta. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. GNE knock-out in mice leads to embryonic lethality, emphasizing the crucial role of this key enzyme for sialic acid biosynthesis. The metabolic capacity to synthesize sialic acid and CMP-sialic acid upon ManNAc loads is amazingly high. An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. Due to the importance of increased concentrations of tumor-surface sialic acid, first attempts to find inhibitors of GNE have been successful.

New insights into the interaction of the key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, with different ligands

2004 ◽  
Vol 2004 (Fall) ◽  
Author(s):  
Astrid Blume ◽  
Andrew J. Benie ◽  
Stephan Hinderlich2 ◽  
Werner Reutter2 ◽  
Richard R. Schmidt3 ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Acid Biosynthesis ◽  
Key Enzyme

The key enzyme of sialic acid biosynthesis (GNE) promotes neurite outgrowth of PC12 cells

Neuroreport ◽  
2008 ◽  
Vol 19 (12) ◽  
pp. 1239-1242 ◽  
Author(s):  
Maria Kontou ◽  
Wenke Weidemann ◽  
Christian Bauer ◽  
Werner Reutter ◽  
Rüdiger Horstkorte
Keyword(s):  
Sialic Acid ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Acid Biosynthesis ◽  
Key Enzyme

scholarly journals Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine

2007 ◽  
Vol 117 (6) ◽  
pp. 1585-1594 ◽  
Author(s):  
Belinda Galeano ◽  
Riko Klootwijk ◽  
Irini Manoli ◽  
MaoSen Sun ◽  
Carla Ciccone ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Acid Biosynthesis ◽  
Glomerular Proteinuria ◽  
Key Enzyme
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