2JFP

Crystal structure of Enterococcus faecalis glutamate racemase in complex with D- Glutamate

Summary for 2JFP

• Entry DOI: 10.2210/pdb2jfp/pdb
• Related: 2JFN 2JFO 2JFQ 2JFU
• Descriptor: GLUTAMATE RACEMASE, D-GLUTAMIC ACID, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: glutamate racemase, peptidoglycan biosynthesis, isomerase
• Biological source: ENTEROCOCCUS FAECALIS
• Total number of polymer chains: 2
• Total formula weight: 63587.50

Authors

Lundqvist, T. (deposition date: 2007-02-03, release date: 2007-07-03, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.98 Å)