2jfo
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Glutamate racemase is an enzyme essential to the bacterial cell wall | + | 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 Structure== | ==About this Structure== | ||
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[[Category: peptidoglycan biosynthesis]] | [[Category: peptidoglycan biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:02:44 2008'' |
Revision as of 16:02, 21 February 2008
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CRYSTAL STRUCTURE OF ENTEROCOCCUS FAECALIS GLUTAMATE RACEMASE IN COMPLEX WITH D- AND L-GLUTAMATE
Overview
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 Structure
2JFO is a Single protein structure of sequence from Enterococcus faecalis with and as ligands. Active as Glutamate racemase, with EC number 5.1.1.3 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 18:02:44 2008
