All known living organisms use L-amino acids as building blocks for ribosomal proteosynthesis. While D-amino acids occur commonly in bacteria, which synthesize and use them, for example during cell wall peptidoglycan biosynthesis, they were considered not to have a role in higher organisms. However, research during the last decade has consistently revealed significant levels of D-serine in mouse and rat brains and D-serine has been found to act as a co-agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptors occurring in the mammalian central nervous system (CNS) NMDA receptor signaling is crucial for many physiological processes in mammals including brain development, learning, and memory. Overactivation of NMDA receptors leads to neuronal death and contributes to post-ischemic brain damage and neuropathologies. Inhibitors of serine racemase are thus putative compounds for the treatment of neurodegeneration, including Alzheimer or Parkinson disease.
The origin of D-Ser in mammals is catalyzed by serine racemase.
In our laboratory, we analyze substrate and reaction specificity
of mSR, design and test inhibitors against the enzyme and in
collaboration with structural biologists aim to solve the 3D
structure of the enzyme by X-ray crystallography.
Selected papers: