2YHW

High-resolution crystal structures of N-Acetylmannosamine kinase: Insights about substrate specificity, activity and inhibitor modelling.

2YHW の概要

• エントリーDOI: 10.2210/pdb2yhw/pdb
• 関連するPDBエントリー: 2YHY 2YI1
• 分子名称: BIFUNCTIONAL UDP-N-ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE, 2-acetamido-2-deoxy-alpha-D-mannopyranose, ZINC ION, ... (10 entities in total)
• 機能のキーワード: transferase, sialic acid, mannac, rok family
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm (By similarity): Q9Y223
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38004.31

構造登録者

Martinez, J.,Nguyen, L.D.,Tauberger, E.,Hinderlich, S.,Zimmer, R.,Tauberger, E.,Reutter, W.,Saenger, W.,Fan, H.,Moniot, S. (登録日: 2011-05-08, 公開日: 2012-02-29, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.64 Å)