2YHY

Structure of N-Acetylmannosamine kinase in complex with N- acetylmannosamine and ADP

Summary for 2YHY

• Entry DOI: 10.2210/pdb2yhy/pdb
• Related: 2YHW 2YI1
• Descriptor: BIFUNCTIONAL UDP-N-ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, CHLORIDE ION, ZINC ION, ... (12 entities in total)
• Functional Keywords: transferase, sugar kinase, sialic acid, rok family
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm (By similarity): Q9Y223
• Total number of polymer chains: 1
• Total formula weight: 38698.11

Authors

Martinez, J.,Nguyen, L.D.,Tauberger, E.,Hinderlich, S.,Reutter, W.,Fan, H.,Saenger, W.,Moniot, S. (deposition date: 2011-05-10, release date: 2012-02-29, Last modification date: 2023-12-20)

Primary citation

Martinez, J.,Nguyen, L.D.,Tauberger, E.,Hinderlich, S.,Reutter, W.,Fan, H.,Saenger, W.,Moniot, S.
Crystal Structures of N-Acetylmannosamine Kinase Provide Insights Into Enzyme Specificity and Inhibition
J.Biol.Chem., 287:13656-, 2012

PubMed Abstract: Sialic acids are essential components of membrane glycoconjugates. They are responsible for the interaction, structure, and functionality of all deuterostome cells and have major functions in cellular processes in health and diseases. The key enzyme of the biosynthesis of sialic acid is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase that transforms UDP-N-acetylglucosamine to N-acetylmannosamine (ManNAc) followed by its phosphorylation to ManNAc 6-phosphate and has a direct impact on the sialylation of cell surface components. Here, we present the crystal structures of the human N-acetylmannosamine kinase (MNK) domain of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase in complexes with ManNAc at 1.64 Å resolution, MNK·ManNAc·ADP (1.82 Å) and MNK·ManNAc 6-phosphate · ADP (2.10 Å). Our findings offer detailed insights in the active center of MNK and serve as a structural basis to design inhibitors. We synthesized a novel inhibitor, 6-O-acetyl-ManNAc, which is more potent than those previously tested. Specific inhibitors of sialic acid biosynthesis may serve to further study biological functions of sialic acid.

PubMed: 22343627
DOI: 10.1074/JBC.M111.318170

Experimental method

X-RAY DIFFRACTION (1.82 Å)