Linked Life Data

19791805

Source:http://linkedlifedata.com/resource/pubmed/id/19791805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2009-10-1
pubmed:abstractText
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. However, specificity studies showed that some of these HAs can act as nonspecific inhibitors of PLP-dependent enzymes. We employed NMR, MS, and UV/vis spectroscopic techniques to reveal that the nonspecific effect is likely due to irreversible interaction of the HA moiety with PLP to form aldoxime species. We also characterize L-aspartic acid beta-hydroxamate as a competitive and selective SR inhibitor that could be used as a scaffold for further inhibitor development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6032-41
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Hydroxamic acids as a novel family of serine racemase inhibitors: mechanistic analysis reveals different modes of interaction with the pyridoxal-5'-phosphate cofactor.
pubmed:affiliation
Gilead Sciences and IOCB Research Center, Institute of Organic Chemistry and Biochemistry of the ASCR, Prague, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't