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NIAID Structure of the Month: Salmonella typhimurium Racemase

Salmonella typhimurium is aGram-negative bacterium that causes disease in the intestinal tract. It is responsible for millions of cases of gastroenteritis every year and can also cause typhoid fever, a life-threatening illness that remains a worldwide health problem.

Bacteria produce a variety of enzymes, including a type known as racemases, which catalyze a chemical reaction that changes the structure of a compound to its mirror image. This process, known as racemization, can convert an L-amino acid into its mirror image: D-amino acid. In bacteria, use of D-amino acids seems to be a common strategy used to adapt to changing environmental conditions. These amino acids may regulate cell wall formation and modification, as well as the production of antimicrobial proteins which kill or slow the growth of other microbes.

There are two kinds of racemases, the pyridoxal 5'-phosphate (PLP)-dependent and PLP-independent. The unique nature and high specificity of the bacterial PLP- independent racemases make them excellent targets for antibacterial drug design.

The Center for Structural Genomics of Infectious Diseases has determined the 1.8 Å resolution crystal structure of PLP-independent aspartate racemase from S. typhimurium in complex with the compound succinate (shown in black). Aspartate racemase has two very similar domains in a pseudo symmetrical arrangement (amino acid residues 1-110 and 215-244 form the N-terminal domain and amino acid residues 111-214 form the C-terminal domain). These domains are situated at approximately 90 degrees to each other. The active site of the protein is located between the domains. Within this structure, succinate is tightly bound in the center of the pseudo-symmetry where two catalytic cystein residues oppose each other with the ligand located between them. The two cysteins work as acid and base for racemization assisted by several other residues.

For more information, please see the Protein Data Bank entry ID 3S7Z.

Salmonella typhimurium racemase

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Last Updated December 01, 2011

Last Reviewed December 01, 2011