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Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes

For a better comprehension of the structure-function relationship in proteins it is necessary to identify the amino acids that are relevant for measurable protein functions. Because of the numerous contacts that amino acids establish within proteins and the cooperative nature of their interactions,...

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Autores principales: García-Torres, Itzhel, Cabrera, Nallely, Torres-Larios, Alfredo, Rodríguez-Bolaños, Mónica, Díaz-Mazariegos, Selma, Gómez-Puyou, Armando, Perez-Montfort, Ruy
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078909/
https://www.ncbi.nlm.nih.gov/pubmed/21533154
http://dx.doi.org/10.1371/journal.pone.0018791
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author García-Torres, Itzhel
Cabrera, Nallely
Torres-Larios, Alfredo
Rodríguez-Bolaños, Mónica
Díaz-Mazariegos, Selma
Gómez-Puyou, Armando
Perez-Montfort, Ruy
author_facet García-Torres, Itzhel
Cabrera, Nallely
Torres-Larios, Alfredo
Rodríguez-Bolaños, Mónica
Díaz-Mazariegos, Selma
Gómez-Puyou, Armando
Perez-Montfort, Ruy
author_sort García-Torres, Itzhel
collection PubMed
description For a better comprehension of the structure-function relationship in proteins it is necessary to identify the amino acids that are relevant for measurable protein functions. Because of the numerous contacts that amino acids establish within proteins and the cooperative nature of their interactions, it is difficult to achieve this goal. Thus, the study of protein-ligand interactions is usually focused on local environmental structural differences. Here, using a pair of triosephosphate isomerase enzymes with extremely high homology from two different organisms, we demonstrate that the control of a seventy-fold difference in reactivity of the interface cysteine is located in several amino acids from two structurally unrelated regions that do not contact the cysteine sensitive to the sulfhydryl reagent methylmethane sulfonate, nor the residues in its immediate vicinity. The change in reactivity is due to an increase in the apparent pKa of the interface cysteine produced by the mutated residues. Our work, which involved grafting systematically portions of one protein into the other protein, revealed unsuspected and multisite long-range interactions that modulate the properties of the interface cysteines and has general implications for future studies on protein structure-function relationships.
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spelling pubmed-30789092011-04-29 Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes García-Torres, Itzhel Cabrera, Nallely Torres-Larios, Alfredo Rodríguez-Bolaños, Mónica Díaz-Mazariegos, Selma Gómez-Puyou, Armando Perez-Montfort, Ruy PLoS One Research Article For a better comprehension of the structure-function relationship in proteins it is necessary to identify the amino acids that are relevant for measurable protein functions. Because of the numerous contacts that amino acids establish within proteins and the cooperative nature of their interactions, it is difficult to achieve this goal. Thus, the study of protein-ligand interactions is usually focused on local environmental structural differences. Here, using a pair of triosephosphate isomerase enzymes with extremely high homology from two different organisms, we demonstrate that the control of a seventy-fold difference in reactivity of the interface cysteine is located in several amino acids from two structurally unrelated regions that do not contact the cysteine sensitive to the sulfhydryl reagent methylmethane sulfonate, nor the residues in its immediate vicinity. The change in reactivity is due to an increase in the apparent pKa of the interface cysteine produced by the mutated residues. Our work, which involved grafting systematically portions of one protein into the other protein, revealed unsuspected and multisite long-range interactions that modulate the properties of the interface cysteines and has general implications for future studies on protein structure-function relationships. Public Library of Science 2011-04-18 /pmc/articles/PMC3078909/ /pubmed/21533154 http://dx.doi.org/10.1371/journal.pone.0018791 Text en García-Torres et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
García-Torres, Itzhel
Cabrera, Nallely
Torres-Larios, Alfredo
Rodríguez-Bolaños, Mónica
Díaz-Mazariegos, Selma
Gómez-Puyou, Armando
Perez-Montfort, Ruy
Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title_full Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title_fullStr Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title_full_unstemmed Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title_short Identification of Amino Acids that Account for Long-Range Interactions in Two Triosephosphate Isomerases from Pathogenic Trypanosomes
title_sort identification of amino acids that account for long-range interactions in two triosephosphate isomerases from pathogenic trypanosomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078909/
https://www.ncbi.nlm.nih.gov/pubmed/21533154
http://dx.doi.org/10.1371/journal.pone.0018791
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