Human serine racemase is nitrosylated at multiple sites.
Biochim Biophys Acta Proteins Proteom
; 1866(7): 813-821, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29410194
ABSTRACT
Serine racemase is a pyridoxal 5'phosphate dependent enzyme responsible for the synthesis of dserine, a neuromodulator of the NMDA receptors. Its activity is modulated by several ligands, including ATP, divalent cations and protein interactors. The murine orthologue is inhibited by S-nitrosylation at Cys113, a residue adjacent to the ATP binding site. We found that the time course of inhibition of human serine racemase by S-nitrosylation is markedly biphasic, with a fast phase associated with the reaction of Cys113. Unlike the murine enzyme, two additional cysteine residues, Cys269, unique to the human orthologue, and Cys128 were also recognized as S-nitrosylation sites through mass spectrometry and site-directed mutagenesis. The effect of S-nitrosylation on the fluorescence of tryptophan residues and on that of the pyridoxal phosphate cofactor indicated that S-nitrosylation produces a partial interruption of the cross-talk between the ATP binding site and the active site. Overall, it appears that the inhibition results from a conformational change rather than the direct displacement of ATP.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Racemases e Epimerases
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article