Disulfide Bridges in the Mesophilic Triosephosphate Isomerase from Giardia lamblia Are Related to Oligomerization and Activity

dc.creatorHORACIO REYES VIVAS
dc.creatorADELAIDA DIAZ VILCHIS
dc.creatorJORGE PEON PERALTA
dc.creatorGUILLERMO MENDOZA HERNANDEZ
dc.creatorJOSE IGNACIO DE LA MORA DE LA MORA
dc.creatorSERGIO ENRIQUEZ FLORES
dc.creatorJULIO LENIN DOMINGUEZ RAMIREZ
dc.creatorGABRIEL LOPEZ VELAZQUEZ
dc.date2007
dc.date.accessioned2023-07-25T16:15:40Z
dc.date.available2023-07-25T16:15:40Z
dc.identifier10.1016/j.jmb.2006.10.053
dc.identifierhttp://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/3124
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7805106
dc.descriptionTriosephosphate 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourceJournal of Molecular Biology 365(3):752 - 763
dc.subjectinfo:eu-repo/classification/cti/3
dc.subjectDimerización
dc.subjectDisulfuros - Metabolismo
dc.subjectGiardia lamblia - Efectos de drogas
dc.subjectGiardia lamblia - Enzimología
dc.subjectProteínas mutantes - Química
dc.subjectProteínas mutantes - Metabolismo
dc.subjectOocistos -Citología
dc.subjectOocistos - Efectos de drogas
dc.subjectOocistos - Enzimología
dc.subjectEstructura cuaternaria de proteína - Efectos de drogas
dc.subjectEstructura secundaria de proteína - Efectos de drogas
dc.subjectEstructura secundaria de proteína - Química
dc.subjectEstructura secundaria de proteína - Metabolismo
dc.subjectTriosa-Fosfato isomerasa - Química
dc.subjectTriosa-Fosfato isomerasa -Metabolismo
dc.subjectTrofozoítos - Citología
dc.subjectTrofozoítos - Efectos de drogas
dc.subjectTrofozoítos -Enzimología
dc.subjectDimerization
dc.subjectDisulfides - Metabolism
dc.subjectGiardia lamblia - Drug effects
dc.subjectGiardia lamblia - Enzymology
dc.subjectMutant proteins - Chemistry
dc.subjectMutant proteins - Metabolism
dc.subjectOocysts - Cytology
dc.subjectOocysts - Drug effects
dc.subjectOocysts - Enzymology
dc.subjectProtein structure, quaternary - Drug effects
dc.subjectProtein structure, secondary - Drug effects
dc.subjectProtein subunits-Chemistry
dc.subjectProtein subunits/metabolism
dc.subjectProtein transport - Drug effects
dc.subjectTriose-Phosphate isomerase/chemistry
dc.subjectTriose-Phosphate isomerase - Metabolism
dc.subjectTrophozoites - Cytology
dc.subjectTrophozoites- Drug effects
dc.subjectTrophozoites- Enzymology
dc.subjectTriosephosphate
dc.subjectDisulfide bonds
dc.subjectGlycolysis
dc.subjectDinamic molecular
dc.titleDisulfide Bridges in the Mesophilic Triosephosphate Isomerase from Giardia lamblia Are Related to Oligomerization and Activity
dc.typeinfo:eu-repo/semantics/article


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