4ZHT

Crystal structure of UDP-GlcNAc 2-epimerase

4ZHT の概要

• エントリーDOI: 10.2210/pdb4zht/pdb
• 分子名称: Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, URIDINE-5'-DIPHOSPHATE, CYTIDINE-5'-MONOPHOSPHATE-5-N-ACETYLNEURAMINIC ACID, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, epimerase, isomerase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9Y223
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 192596.48

構造登録者

Chen, S.C.,Yang, C.S.,Ko, T.P.,Chen, Y. (登録日: 2015-04-27, 公開日: 2016-06-01, 最終更新日: 2024-11-13)

主引用文献

Chen, S.C.,Huang, C.H.,Lai, S.J.,Yang, C.S.,Hsiao, T.H.,Lin, C.H.,Fu, P.K.,Ko, T.P.,Chen, Y.
Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis.
Sci Rep, 6:23274-23274, 2016

PubMed Abstract: The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production. It is different from the non-hydrolyzing enzymes for bacterial cell wall biosynthesis, and it is feed-back inhibited by the downstream product CMP-Neu5Ac. Here the complex crystal structure of the N-terminal epimerase part of human GNE shows a tetramer in which UDP binds to the active site and CMP-Neu5Ac binds to the dimer-dimer interface. The enzyme is locked in a tightly closed conformation. By comparing the UDP-binding modes of the non-hydrolyzing and hydrolyzing UDP-GlcNAc epimerases, we propose a possible explanation for the mechanistic difference. While the epimerization reactions of both enzymes are similar, Arg113 and Ser302 of GNE are likely involved in product hydrolysis. On the other hand, the CMP-Neu5Ac binding mode clearly elucidates why mutations in Arg263 and Arg266 can cause sialuria. Moreover, full-length modelling suggests a channel for ManNAc trafficking within the bifunctional enzyme.

PubMed: 26980148
DOI: 10.1038/srep23274

実験手法

X-RAY DIFFRACTION (2.69 Å)