Título
Disulfide Bridges in the Mesophilic Triosephosphate Isomerase from Giardia lamblia Are Related to Oligomerization and Activity
Autor
HORACIO REYES VIVAS
ADELAIDA DIAZ VILCHIS
JORGE PEON PERALTA
GUILLERMO MENDOZA HERNANDEZ
JOSE IGNACIO DE LA MORA DE LA MORA
SERGIO ENRIQUEZ FLORES
JULIO LENIN DOMINGUEZ RAMIREZ
GABRIEL LOPEZ VELAZQUEZ
Nivel de Acceso
Acceso Abierto
Materias
MEDICINA Y CIENCIAS DE LA SALUD - (CTI) Dimerización - ([Journal of Molecular Biology 365(3):752 - 763]) Disulfuros - Metabolismo - ([Journal of Molecular Biology 365(3):752 - 763]) Giardia lamblia - Efectos de drogas - ([Journal of Molecular Biology 365(3):752 - 763]) Giardia lamblia - Enzimología - ([Journal of Molecular Biology 365(3):752 - 763]) Proteínas mutantes - Química - ([Journal of Molecular Biology 365(3):752 - 763]) Proteínas mutantes - Metabolismo - ([Journal of Molecular Biology 365(3):752 - 763]) Oocistos -Citología - ([Journal of Molecular Biology 365(3):752 - 763]) Oocistos - Efectos de drogas - ([Journal of Molecular Biology 365(3):752 - 763]) Oocistos - Enzimología - ([Journal of Molecular Biology 365(3):752 - 763]) Estructura cuaternaria de proteína - Efectos de drogas - ([Journal of Molecular Biology 365(3):752 - 763]) Estructura secundaria de proteína - Efectos de drogas - ([Journal of Molecular Biology 365(3):752 - 763]) Estructura secundaria de proteína - Química - ([Journal of Molecular Biology 365(3):752 - 763]) Estructura secundaria de proteína - Metabolismo - ([Journal of Molecular Biology 365(3):752 - 763]) Triosa-Fosfato isomerasa - Química - ([Journal of Molecular Biology 365(3):752 - 763]) Triosa-Fosfato isomerasa -Metabolismo - ([Journal of Molecular Biology 365(3):752 - 763]) Trofozoítos - Citología - ([Journal of Molecular Biology 365(3):752 - 763]) Trofozoítos - Efectos de drogas - ([Journal of Molecular Biology 365(3):752 - 763]) Trofozoítos -Enzimología - ([Journal of Molecular Biology 365(3):752 - 763]) Dimerization - ([Journal of Molecular Biology 365(3):752 - 763]) Disulfides - Metabolism - ([Journal of Molecular Biology 365(3):752 - 763]) Giardia lamblia - Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) Giardia lamblia - Enzymology - ([Journal of Molecular Biology 365(3):752 - 763]) Mutant proteins - Chemistry - ([Journal of Molecular Biology 365(3):752 - 763]) Mutant proteins - Metabolism - ([Journal of Molecular Biology 365(3):752 - 763]) Oocysts - Cytology - ([Journal of Molecular Biology 365(3):752 - 763]) Oocysts - Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) Oocysts - Enzymology - ([Journal of Molecular Biology 365(3):752 - 763]) Protein structure, quaternary - Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) Protein structure, secondary - Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) Protein subunits-Chemistry - ([Journal of Molecular Biology 365(3):752 - 763]) metabolism - ([Journal of Molecular Biology 365(3):752 - 763]) Protein transport - Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) chemistry - ([Journal of Molecular Biology 365(3):752 - 763]) Triose-Phosphate isomerase - Metabolism - ([Journal of Molecular Biology 365(3):752 - 763]) Trophozoites - Cytology - ([Journal of Molecular Biology 365(3):752 - 763]) Trophozoites- Drug effects - ([Journal of Molecular Biology 365(3):752 - 763]) Trophozoites- Enzymology - ([Journal of Molecular Biology 365(3):752 - 763]) Triosephosphate - ([Journal of Molecular Biology 365(3):752 - 763]) Disulfide bonds - ([Journal of Molecular Biology 365(3):752 - 763]) Glycolysis - ([Journal of Molecular Biology 365(3):752 - 763]) Dinamic molecular - ([Journal of Molecular Biology 365(3):752 - 763])
Resumen o descripción
Triosephosphate isomerase from the mesophile Giardia lamblia (GlTIM) is the only known TIM with natural disulfide bridges. We previously found that oxidized and reduced thiol states of GlTIM are involved in the interconversion between native dimers and higher oligomeric species, and in the regulation of enzymatic activity. Here, we found that trophozoites and cysts have different oligomeric species of GlTIM and complexes of GlTIM with other proteins. Our data indicate that the internal milieu of G. lamblia is favorable for the formation of disulfide bonds. Enzyme mutants of the three most solvent exposed Cys of GlTIM (C202A, C222A, and C228A) were prepared to ascertain their contribution to oligomerization and activity. The data show that the establishment of a disulfide bridge between two C202 of two dimeric GlTIMs accounts for multimerization. In addition, we found that the establishment of an intramonomeric disulfide bond between C222 and C228 abolishes catalysis. Multimerization and inactivation are both reversed by reducing conditions. The 3D structure of the C202A GlTIM was solved at 2.1 Å resolution, showing that the environment of the C202 is prone to hydrophobic interactions. Molecular dynamics of an in silico model of GlTIM when the intramonomeric disulfide bond is formed, showed that S216 is displaced 4.6 Å from its original position, causing loss of hydrogen bonds with residues of the active-site loop. This suggests that this change perturb the conformational state that aligns the catalytic center with the substrate, inducing enzyme inactivation. © 2006 Elsevier Ltd. All rights reserved.
Editor
Elsevier
Fecha de publicación
2007
Tipo de publicación
Artículo
Recurso de información
http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/3124
10.1016/j.jmb.2006.10.053
Formato
application/pdf
Fuente
Journal of Molecular Biology 365(3):752 - 763
Idioma
Inglés
Repositorio Orígen
Repositorio del Instituto Nacional de Pediatría
Descargas
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