Novel protein-protein interaction between spermidine synthase and S-adenosylmethionine decarboxylase from Leishmania donovani.
Biochem Biophys Res Commun
; 456(2): 637-42, 2015 Jan 09.
Article
en En
| MEDLINE
| ID: mdl-25511700
ABSTRACT
Polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including Leishmania. S-adenosylmethionine decarboxylase (AdoMetDc) and spermidine synthase (SpdSyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated S-adenosylmethionine (dcSAM), acting as an aminopropyl donor for the latter enzyme. Here we have explored the possibility of and identified the protein-protein interaction between SpdSyn and AdoMetDc. The protein-protein interaction has been identified using GST pull down assay. Isothermal titration calorimetry reveals that the interaction is thermodynamically favorable. Fluorescence spectroscopy studies also confirms the interaction, with SpdSyn exhibiting a change in tertiary structure with increasing concentrations of AdoMetDc. Size exclusion chromatography suggests the presence of the complex as a hetero-oligomer. Taken together, these results suggest that the enzymes indeed form a heteromer. Computational analyses suggest that this complex differs significantly from the corresponding human complex, implying that this complex could be a better therapeutic target than the individual enzymes.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Espermidina Sintasa
/
Adenosilmetionina Descarboxilasa
/
Leishmania donovani
/
Proteínas Protozoarias
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2015
Tipo del documento:
Article
País de afiliación:
India