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Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México, DGAPA, UNAM: G27551
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funding vehicle for: Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface

Consejo Nacional de Ciencia y Tecnología, CONACYT: IN214202
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type: BFO_0000020
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type: Grant
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funding vehicle for: Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface

Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface
type: Generically Dependent Continuant
has funding vehicle: Consejo Nacional de Ciencia y Tecnología, CONACYT: IN214202
abstract: We characterized by crystallographic, calorimetric and biochemical methods the action of a low molecular weight compound, 3-(2-benzothiazolylthio)-1- propanesulfonic acid (compound 8) that binds to the dimer interface of triosephosphate isomerase from Trypanosoma cruzi (TcTIM) and thereby abolishes its function with a high level of selectivity. The kinetics of TcTIM inactivation by the agent and isothermal titration calorimetry experiments showed that the binding of two molecules of the compound per enzyme is needed for inactivation. The binding of the first molecule is endothermic, and that of the second exothermic. Crystals of TcTIM in complex with one molecule of the inactivating agent that diffracted to a resolution of 2 Å were obtained. The compound is at the dimer interface at less than 4 Å from residues of the two subunits. Compound 8 is more effective at low than at high protein concentrations, indicating that it perturbs the association between the two TcTIM monomers. Calorimetric and kinetic data of experiments in which TcTIM was added to a solution of the inactivating agent showed that at low concentrations of the compound, inactivation is limited by binding, whereas at high concentrations of the agent, the events that follow binding become rate-limiting. The portion of the interface of TcTIM that binds the benzothiazole derivative and its equivalent region in human TIM differs in amino acid composition and hydrophobic packing. Thus, we show that by focusing on protein-protein interfaces, it is possible to discover low molecular weight compounds that are selective for enzymes from parasites. © 2004 Elsevier Ltd. All rights reserved.
type: Information Content Entity
type: Continuant
related by: authorship 8014
has funding vehicle: Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México, DGAPA, UNAM: G27551
related by: authorship 8012
most specific type: Article
e iscopus: 2-s2.0-4143068388
page start: 1355
type: Document
pmid: 15321726
related by: authorship 8008
related by: authorship 8010
related by: authorship 8015
type: Article
related by: authorship 8013
freetext keyword: benzothiazole; interface perturbers; protein-protein interfaces; triosephosphate isomerase; Trypanosoma cruzi 3 (2 benzothiazolylthio) 1 propanesulfonic acid; benzothiazole derivative; dimer; microbial enzyme; triosephosphate isomerase; unclassified drug; amino acid composition; article; binding affinity; calorimetry; chemical binding; controlled study; crystal structure; dimerization; enzyme activity; enzyme analysis; enzyme inactivation; enzyme inhibition; enzyme kinetics; enzyme mechanism; hydrophobicity; isotherm; molecular weight; nonhuman; priority journal; protozoon; sequence homology; titrimetry; Trypanosoma cruzi; X ray crystallography; Trypanosoma; Trypanosoma cruzi
origen: scopus
type: Entity
most specific type: Document
has publication venue: Journal of Molecular Biology
related by: authorship 8009
chemicalscas: triosephosphate isomerase, 9023-78-3
type: Thing
related by: authorship 8011
doi: 10.1016/j.jmb.2004.06.056
date time value: article date 1349
related by: authorship 8007
crisid: 1349
issue: 5
volume: 341
estado: published
page end: 1365

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RDF description of Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface - http://orbis.uaslp.mx/vivo/individual/scopus1348
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date: 2026-08-27T06:31:04
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Journal of Molecular Biology
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publication venue for: Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface
type: Generically Dependent Continuant
type: Document

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