Crystallization and preliminary X-ray crystallographic studies of glutamate racemase from<i>Lactobacillus fermenti</i>

Lee, Ki Seog; Park, Seon Mi; Hwang, Kwang Yeon; Min, Young

doi:10.1107/s1744309104034426

Cited by 2 publications

(2 citation statements)

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“…However, no strong interactions between d -glutamine and the amino acid residues present in the active site were noticed. In 2005, it was reported the crystal structure of the GluR from L. fermenti, which shares approximately 32% sequence identity with A. pyrophilus GluR. It represents the first three-dimensional structure of a cofactor-independent racemase from a Gram-positive bacterium.…”

Section: Amino Acid Racemases As Drug Targetsmentioning

confidence: 99%

Drug Discovery Targeting Amino Acid Racemases

Conti¹,

Tamborini²,

Pinto³

et al. 2011

Chem. Rev.

113

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Amino acids are among the most important molecules in nature since they play central roles both as building blocks of proteins and as intermediates in metabolism. The amino acid sequence dictates protein folding, the native three dimensional structure, and protein stability. Furthermore, the peculiar chemical properties of the amino acids forming the active site and their interplay determine protein function and regulation. All amino acids found in proteins, except glycine, possess a stereogenic center at the a-carbon atom. Millions of years of evolution have resulted in the virtually complete homochirality of such a stereogenic center, i.e. the L-enantiomer, in mammals. 1 This selection of the L-amino acids by nature is generally considered to be a result of chance. 2 Since the cornerstone of the protein-ligand recognition is the multi-point attachment theory, it turns out that the configuration of the a-carbon atom of amino acids strongly affects the protein-ligand interaction. Nevertheless, during the last half of the twentieth century, various studies evidenced the presence of Damino acids in some plants and bacteria. 3,4 These compounds were either found in a free state or in peptides and proteins. Most bacteria produce significant amounts of D-alanine (D-Ala) and D-glutamate (D-Glu), which are incorporated into peptidoglycan. 5 Peptidoglycan is a strong and elastic polymer of the bacterial wall, which is capable to counteract the osmotic pressure of the cell, maintaining cell shape and anchoring components of the cell envelope. 6 The number of D-amino acids present in the structure of peptidoglycan seems to constitute a measure of protection against peptidase and protease attacks. So far, no peptidase capable of hydrolyzing a peptide bond characterized by the sequence D-D or D-L amino acids has been isolated in mammals. In addition, several antibiotics produced by prokaryotes (e.g. bacitracin, actinomycin D) contain D-amino acids (Figure 1). It has been recently demonstrated that bacteria synthesize a pool of different D-amino acids, including D-methionine (D-Met) and D-leucine (D-Leu) in Vibrio cholerae and D-tyrosine (D-Tyr) and D-phenylalanine (D-Phe) in Bacillus subtilis. By selectively incorporating them in the peptidoglycan cell wall, bacteria cope to different environmental stresses. 7

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Section: Amino Acid Racemases As Drug Targetsmentioning

confidence: 99%

Drug Discovery Targeting Amino Acid Racemases

Conti¹,

Tamborini²,

Pinto³

et al. 2011

Chem. Rev.

113

View full text Add to dashboard Cite

show abstract

“…32 Since the interactions seen in GluR interface are of side-chain atoms and ApGluR exhibited a totally different dimeric form, the result obtained with L. fermenti is of interest. 33 The active site…”

Section: Dimeric Arrangement Of Spglurmentioning

confidence: 99%