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Título : Disulfide Bridges in the Mesophilic Triosephosphate Isomerase from Giardia lamblia Are Related to Oligomerization and Activity
Creador: 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
Palabras clave : MEDICINA Y CIENCIAS DE LA SALUD
Dimerización
Disulfuros - Metabolismo
Giardia lamblia - Efectos de drogas
Giardia lamblia - Enzimología
Proteínas mutantes - Química
Proteínas mutantes - Metabolismo
Oocistos -Citología
Oocistos - Efectos de drogas
Oocistos - Enzimología
Estructura cuaternaria de proteína - Efectos de drogas
Estructura secundaria de proteína - Efectos de drogas
Estructura secundaria de proteína - Química
Estructura secundaria de proteína - Metabolismo
Triosa-Fosfato isomerasa - Química
Triosa-Fosfato isomerasa -Metabolismo
Trofozoítos - Citología
Trofozoítos - Efectos de drogas
Trofozoítos -Enzimología
Dimerization
Disulfides - Metabolism
Giardia lamblia - Drug effects
Giardia lamblia - Enzymology
Mutant proteins - Chemistry
Mutant proteins - Metabolism
Oocysts - Cytology
Oocysts - Drug effects
Oocysts - Enzymology
Protein structure, quaternary - Drug effects
Protein structure, secondary - Drug effects
Protein subunits-Chemistry
Protein subunits/metabolism
Protein transport - Drug effects
Triose-Phosphate isomerase/chemistry
Triose-Phosphate isomerase - Metabolism
Trophozoites - Cytology
Trophozoites- Drug effects
Trophozoites- Enzymology
Triosephosphate
Disulfide bonds
Glycolysis
Dinamic molecular
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.
Editorial : Elsevier
Fecha de publicación : 2007
Tipo de publicación: Artículo
Formato: Adobe PDF
Identificador del Recurso : 10.1016/j.jmb.2006.10.053
Fuente: Journal of Molecular Biology 365(3):752 - 763
URI : http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/3124
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