Structural Basis for Glutamate Racemase Inhibition

Crystal Structure of Diaminopimelate Epimerase from Arabidopsis thaliana, an Amino Acid Racemase Critical for l-Lysine Biosynthesis

“…In the recent past, crystal structures have been reported for some of the bacterial PLP-independent racemases including glutamate racemase, [18][19][20][21][22] aspartate racemase, 23,24 proline racemase, 25 and an inactive form of DAP epimerase. 26,27 In earlier work, we reported the crystal structures of bacterial DAP epimerase from Haemophilus influenzae with two different isomers of the irreversible inhibitor 2-(4-amino-4-carboxybutyl)-aziridine-2-carboxylate (AziDAP) 28,29 as well as of variants that have an active-site cysteine to serine substitution.…”

Biochemical Characterization of Glutamate Racemase—A New Candidate Drug Target against Burkholderia cenocepacia Infections

“…Previous reports indicate that GR oligomerization critically depends on electrostatic interactions on the enzyme surface, and also on the absence or presence of substrate. Notably, numerous different dimerization interfaces were proposed, involving so-called head-to-head or tail-to-tail interactions [12, 18, 19, 21, 42–44]. Despite numerous crystallization attempts, we could not obtain experimental structural information of Bc GR either in absence nor in presence of the inhibitors.…”

“…The quaternary structure of glutamate racemases is different in various bacteria, being monomeric [13], dimeric [19, 42], or in an equilibrium between these two states [42, 43]. Previous reports indicate that GR oligomerization critically depends on electrostatic interactions on the enzyme surface, and also on the absence or presence of substrate.…”

“…Structural and functional studies of GR from different bacteria, including Helicobacter pylori [17], Bacillus subtilis [18], Streptococcus pyogenes [19], Lactobacillus brevis [20], Aquifex pyrophilus [12] and Bacillus anthracis [21], revealed a high divergence among glutamate racemase enzymes. In fact, several different drugs have been reported as GR inhibitors, such as pyrazolopyrimidinediones [13], pyridodiazepine amines [17], 8-benzyl pteridine-6,7-diones [22], dipicolinate and benzoat-3-sulfonate [23], (2R,4S)-4-substituted D-glutamate analogs [18], 1-H-benzimidazole-2-sulfonic acid [24], 2,6 pyridinedicarboxylic acid [23, 25] and 4-hydroxybenzene-1,3-disulfonate [26].…”

Evaluation of new antimicrobial agents on Bacillus spp. strains: docking affinity and in vitro inhibition of glutamate-racemase

“…On the other hand, boron-containing compounds are antimicrobial and anticancer agents as well as inhibitors of several different enzymes 6,7 . Amino acids constitute one type of natural substrate that has been used for many years as the starting material for the development of antimicrobial agents 8,9 . Whereas l-amino acids are used by eukaryotes, d-amino acids are important for the bacterial cell wall formation.…”