3JUJ

The crystal structure of apo- UDP-glucose pyrophosphorylase

3JUJ の概要

• エントリーDOI: 10.2210/pdb3juj/pdb
• 関連するPDBエントリー: 3JUK
• 分子名称: UDP-glucose pyrophosphorylase (GalU) (2 entities in total)
• 機能のキーワード: udp-glucose pyrophosphorylase, helicobacter pylori, transferase
• 由来する生物種: Helicobacter pylori (Campylobacter pylori)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 128347.73

構造登録者

Kim, H.,Kim, K.K. (登録日: 2009-09-15, 公開日: 2010-03-31, 最終更新日: 2024-03-20)

主引用文献

Kim, H.,Choi, J.,Kim, T.,Lokanath, N.K.,Ha, S.C.,Suh, S.W.,Hwang, H.-Y.,Kim, K.K.
Structural basis for the reaction mechanism of UDP-glucose pyrophosphorylase
Mol.Cells, 29:397-405, 2010

PubMed Abstract: UDP-glucose pyrophosphorylases (UGPase; EC 2.7.7.9) catalyze the conversion of UTP and glucose-1-phosphate to UDP-glucose and pyrophosphate and vice versa. Prokaryotic UGPases are distinct from their eukaryotic counterparts and are considered appropriate targets for the development of novel antibacterial agents since their product, UDP-glucose, is indispensable for the biosynthesis of virulence factors such as lipopolysaccharides and capsular polysaccharides. In this study, the crystal structures of UGPase from Helicobacter pylori (HpUGPase) were determined in apo- and UDP-glucose/Mg(2+)-bound forms at 2.9 A and 2.3 A resolutions, respectively. HpUGPase is a homotetramer and its active site is located in a deep pocket of each subunit. Magnesium ion is coordinated by Asp130, two oxygen atoms of phosphoryl groups, and three water molecules with octahedral geometry. Isothermal titration calorimetry analyses demonstrated that Mg(2+) ion plays a key role in the enzymatic activity of UGPase by enhancing the binding of UGPase to UTP or UDP-glucose, suggesting that this reaction is catalyzed by an ordered sequential Bi Bi mechanism. Furthermore, the crystal structure explains the specificity for uracil bases. The current structural study combined with functional analyses provides essential information for understanding the reaction mechanism of bacterial UGPases, as well as a platform for the development of novel antibacterial agents.

PubMed: 20238176
DOI: 10.1007/s10059-010-0047-6

実験手法

X-RAY DIFFRACTION (2.9 Å)