Hydroxamic acids as a novel family of serine racemase inhibitors: Mechanistic analysis reveals different modes of interaction with the pyridoxal-5'-phosphate cofactor

0330745 - ÚOCHB 2010 RIV US eng J - Journal Article
Hoffman, Hillary Elizabeth - Jirásková, Jana - Cígler, Petr - Šanda, Miloslav - Schraml, Jan - Konvalinka, Jan
Hydroxamic acids as a novel family of serine racemase inhibitors: Mechanistic analysis reveals different modes of interaction with the pyridoxal-5'-phosphate cofactor.
Journal of Medicinal Chemistry. Roč. 52, č. 19 (2009), s. 6032-6041. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA MŠMT 1M0508; GA AV ČR IAA400720706
Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z40720504
Keywords : hydroxamic acids * serine racemase * d-serine * pyridoxal-5'-phosphate
Subject RIV: CE - Biochemistry
Impact factor: 4.802, year: 2009

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.
Permanent Link: http://hdl.handle.net/11104/0176459