Structural and biochemical studies on the role of active site Thr166 and Asp236 in the catalytic function of D-Serine deaminase from Salmonella typhimurium.
Biochem Biophys Res Commun
; 504(1): 40-45, 2018 09 26.
Article
en En
| MEDLINE
| ID: mdl-30173889
ABSTRACT
D-Serine deaminase (DSD) degrades D-Ser to pyruvate and ammonia. Uropathogenic bacteria survive in the toxic D-Ser containing mammalian urine because of DSD activity. The crystal structure of the apo form of Salmonella typhimurium DSD (StDSD) has been reported earlier. In the present work, we have investigated the role of two active site residues, Thr166 and Asp236 by site directed mutagenesis (T166A and D236L). The enzyme activity is lost upon mutation of these residues. The 2.7â¯Å resolution crystal structure of T166A DSD with bound PLP reported here represents the first structure of the holo form of StDSD. PLP binding induces small changes in the relative dispositions of the minor and major domains of the protein and this inter-domain movement becomes substantial upon interaction with the substrate. The conformational changes bring Thr166 to a position at the active site favorable for the degradation of D-Ser. Examination of the different forms of the enzyme and comparison with structures of homologous enzymes suggests that Thr166 is the most probable base abstracting proton from the Cα atom of the substrate and Asp236 is crucial for binding of the cofactor.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Salmonella typhimurium
/
L-Serina Deshidratasa
/
Treonina
/
Ácido Aspártico
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
País de afiliación:
India