Hydroxamic acids as a novel family of serine racemase inhibitors: Mechanistic analysis reveals different modes of interaction with the pyridoxal-5'-phosphate cofactor
2009
Abstract
Mammalian serine racemase (SR) is a pyridoxal-5′-phosphate (PLP) dependent enzyme responsible for the biosynthesis of the neurotransmitter d-serine, which activates N-methyl-d-aspartate (NMDA) receptors in the CNS. Aberrant regulation of NMDA receptor signaling has been implicated in a variety of neuropathologies, and inhibitors of SR would therefore be a worthwhile tool for further investigation or treatment of such conditions.
Here, we identify a series of small aliphatic hydroxamic acids (HAs) that act as potent SR inhibitors and present a detailed analysis of there mechanism of action.