Kim, Hun and Choi, Jongkeun and Kim, Truc and Lokanath, N. K. and Ha, Sung Chul and Suh, Se Won and Hwang, Hye-Yeon and Kim, Kyeong Kyu (2010) Structural basis for the reaction mechanism of UDP-glucose pyrophosphorylase. Molecules and Cells, 29 (4). pp. 397-405. ISSN 0219-1032
Full text not available from this repository. (Request a copy)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/Mg2+-bound forms at 2.9 Å and 2.3 Å 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 Mg2+ 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.
| Item Type: | Article |
|---|---|
| Subjects: | D Physical Science > Physics |
| Divisions: | Department of > Physics |
| Depositing User: | LA manjunath user |
| Date Deposited: | 15 Jul 2019 10:10 |
| Last Modified: | 16 Nov 2019 10:27 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/5204 |
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