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'''CRYSTAL STRUCTURE OF HELICOBACTER PYLORI GLUTAMATE RACEMASE IN COMPLEX WITH D-GLUTAMATE''' | '''CRYSTAL STRUCTURE OF HELICOBACTER PYLORI GLUTAMATE RACEMASE IN COMPLEX WITH D-GLUTAMATE''' | ||
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[[Category: Lundqvist, T.]] | [[Category: Lundqvist, T.]] | ||
[[Category: Xue, Y.]] | [[Category: Xue, Y.]] | ||
[[Category: | [[Category: Cell shape]] | ||
[[Category: | [[Category: Cell wall]] | ||
[[Category: | [[Category: Glutamate racemase]] | ||
[[Category: | [[Category: Isomerase]] | ||
[[Category: | [[Category: Peptidoglycan biosynthesis]] | ||
[[Category: | [[Category: Peptidoglycan synthesis]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:51:11 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 08:51, 4 May 2008
CRYSTAL STRUCTURE OF HELICOBACTER PYLORI GLUTAMATE RACEMASE IN COMPLEX WITH D-GLUTAMATE
OverviewOverview
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.
About this StructureAbout this Structure
2JFX is a Single protein structure of sequence from Helicobacter pylori. Full crystallographic information is available from OCA.
ReferenceReference
Exploitation of structural and regulatory diversity in glutamate racemases., Lundqvist T, Fisher SL, Kern G, Folmer RH, Xue Y, Newton DT, Keating TA, Alm RA, de Jonge BL, Nature. 2007 Jun 14;447(7146):817-22. PMID:17568739 Page seeded by OCA on Sun May 4 08:51:11 2008