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A competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase

dc.contributor.authorJiménez Sandoval, Pedro
dc.contributor.authorVique Sánchez, José Luis
dc.contributor.authorLópez Hidalgo, Marisol
dc.contributor.authorVelázquez Juárez, Gilberto
dc.contributor.authorDíaz Quezada, Corina
dc.contributor.authorArroyo Navarro, Luis Fernando
dc.contributor.authorMontero Morán, Gabriela Margarita
dc.contributor.authorFattori, Juliana
dc.contributor.authorDíaz Salazar, Alma Jessica
dc.contributor.authorRudiño Piñera, Enrique
dc.contributor.authorSotelo Mundo, Rogerio Rafael
dc.contributor.authorMigliorini Figueira, Ana Carolina
dc.contributor.authorLara González, Samuel
dc.contributor.authorBenítez Cardoza, Claudia Guadalupe
dc.contributor.authorBrieba de Castro, Luis Gabriel
dc.date.accessioned2019-08-23T22:04:47Z
dc.date.available2019-08-23T22:04:47Z
dc.date.issued2017
dc.identifier.citationPedro Jimenez-Sandoval, Jose Luis Vique-Sanchez, Marisol López Hidalgo, Gilberto Velazquez-Juarez, Corina Diaz-Quezada, Luis Fernando Arroyo-Navarro, Gabriela Montero Moran, Juliana Fattori, A. Jessica Diaz-Salazar, Enrique Rudiño-Pinera, Rogerio Sotelo-Mundo, Ana Carolina Migliorini Figueira, Samuel Lara-Gonzalez, Claudia G. Benítez-Cardoza, Luis G. Brieba, A competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1865, Issue 11, Part A, 2017, Pages 1423-1432
dc.identifier.urihttp://hdl.handle.net/11627/5103
dc.description.abstract"The protozoan parasite Trichomonas vaginalis contains two nearly identical triosephosphate isomerases (TvTIMs) that dissociate into stable monomers and dimerize upon substrate binding. Herein, we compare the role of the “ball and socket” and loop 3 interactions in substrate assisted dimer assembly in both TvTIMs. We found that point mutants at the “ball” are only 39 and 29-fold less catalytically active than their corresponding wild-type counterparts, whereas ?loop 3 deletions are 1502 and 9400-fold less active. Point and deletion mutants dissociate into stable monomers. However, point mutants assemble as catalytic competent dimers upon binding of the transition state substrate analog PGH, whereas loop 3 deletions remain monomeric. A comparison between crystal structures of point and loop 3 deletion monomeric mutants illustrates that the catalytic residues in point mutants and wild-type TvTIMs are maintained in the same orientation, whereas the catalytic residues in deletion mutants show an increase in thermal mobility and present structural disorder that may hamper their catalytic role. The high enzymatic activity present in monomeric point mutants correlates with the formation of dimeric TvTIMs upon substrate binding. In contrast, the low activity and lack of dimer assembly in deletion mutants suggests a role of loop 3 in promoting the formation of the active site as well as dimer assembly. Our results suggest that in TvTIMs the active site is assembled during dimerization and that the integrity of loop 3 and ball and socket residues is crucial to stabilize the dimer."
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectDimer assembly
dc.subjectTriosephosphate isomerase
dc.subjectTrichomonas
dc.subjectX-ray crystallography
dc.subject.classificationBIOLOGÍA MOLECULAR
dc.titleA competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase
dc.typearticle
dc.identifier.doihttps://doi.org/10.1016/j.bbapap.2017.07.014
dc.rights.accessAcceso Abierto


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional