2JFX

Crystal structure of Helicobacter pylori glutamate racemase in complex with D-Glutamate

2JFX の概要

• エントリーDOI: 10.2210/pdb2jfx/pdb
• 関連するPDBエントリー: 2JFY
• 分子名称: GLUTAMATE RACEMASE, D-GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: cell wall, isomerase, cell shape, glutamate racemase, peptidoglycan synthesis, peptidoglycan biosynthesis
• 由来する生物種: HELICOBACTER PYLORI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57358.64

構造登録者

Xue, Y.,Lundqvist, T. (登録日: 2007-02-06, 公開日: 2007-07-03, 最終更新日: 2024-05-08)

主引用文献

Lundqvist, T.,Fisher, S.L.,Kern, G.,Folmer, R.H.A.,Xue, Y.,Newton, D.T.,Keating, T.A.,Alm, R.A.,De Jonge, B.L.M.
Exploitation of Structural and Regulatory Diversity in Glutamate Racemases
Nature, 447:817-, 2007

PubMed Abstract: Glutamate racemase is an enzyme essential to the bacterial cell wall biosynthesis pathway, and has therefore been considered as a target for antibacterial drug discovery. We characterized the glutamate racemases of several pathogenic bacteria using structural and biochemical approaches. Here we describe three distinct mechanisms of regulation for the family of glutamate racemases: allosteric activation by metabolic precursors, kinetic regulation through substrate inhibition, and D-glutamate recycling using a d-amino acid transaminase. In a search for selective inhibitors, we identified a series of uncompetitive inhibitors specifically targeting Helicobacter pylori glutamate racemase that bind to a cryptic allosteric site, and used these inhibitors to probe the mechanistic and dynamic features of the enzyme. These structural, kinetic and mutational studies provide insight into the physiological regulation of these essential enzymes and provide a basis for designing narrow-spectrum antimicrobial agents.

PubMed: 17568739
DOI: 10.1038/NATURE05689

実験手法

X-RAY DIFFRACTION (2.3 Å)