2JFZ: Crystal Structure Of Helicobacter Pylori Glutamate Racemase In Complex With D-Glutamate And An Inhibitor

Citation:
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.
PDB ID: 2JFZDownload
MMDB ID: 47182
PDB Deposition Date: 2007/2/6
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.86  Å
Source Organism:
Similar Structures:
Biological Unit for 2JFZ: dimeric; determined by author and by software (PQS)
Molecular Components in 2JFZ
Label Count Molecule
Proteins (2 molecules)
2
Glutamate Racemase
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

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