Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor

Lectins are able to recognize specific carbohydrate structures through their carbohydrate recognition domain (CRD). The lectin from the mushroom Agaricus bisporus (ABL) has the remarkable ability of selectively recognizing the TF-antigen, composed of Galβ1-3GalNAc, Ser/Thr linked to proteins, specif...

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Autores principales:	Gauto, D.F., Di Lella, S., Estrin, D.A., Monaco, H.L., Martí, M.A.
Formato:	JOUR
Materias:	Affinity Carbohydrate recognition domain Lectin Molecular dynamics Selectivity Solvent structure Antigens Carbohydrates Glucose Ligands Solvents Tissue Troposphere Crystal structure Agaricus bisporus lectin lectin n acetylgalactosamine unclassified drug Agaricus bisporus article carbohydrate recognition domain complex formation controlled study crystal structure epimer hydrogen bond lectin binding lectin binding site ligand binding molecular dynamics molecular model molecular recognition priority journal protein domain thermodynamics Acetylgalactosamine Acetylglucosamine Agaricus Antigens, Tumor-Associated, Carbohydrate Binding Sites Carbohydrate Conformation Hydrogen Bonding Lectins Molecular Dynamics Simulation Protein Binding Thermodynamics Basidiomycota
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00086215_v346_n7_p939_Gauto
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00086215_v346_n7_p939_Gauto2023-10-03T14:07:25Z Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor Gauto, D.F. Di Lella, S. Estrin, D.A. Monaco, H.L. Martí, M.A. Affinity Carbohydrate recognition domain Lectin Molecular dynamics Selectivity Solvent structure Affinity Carbohydrate recognition domain Lectin Selectivity Solvent structure Antigens Carbohydrates Glucose Ligands Molecular dynamics Solvents Tissue Troposphere Crystal structure Agaricus bisporus lectin lectin n acetylgalactosamine unclassified drug Agaricus bisporus article carbohydrate recognition domain complex formation controlled study crystal structure epimer hydrogen bond lectin binding lectin binding site ligand binding molecular dynamics molecular model molecular recognition priority journal protein domain thermodynamics Acetylgalactosamine Acetylglucosamine Agaricus Antigens, Tumor-Associated, Carbohydrate Binding Sites Carbohydrate Conformation Hydrogen Bonding Lectins Molecular Dynamics Simulation Protein Binding Thermodynamics Agaricus bisporus Basidiomycota Lectins are able to recognize specific carbohydrate structures through their carbohydrate recognition domain (CRD). The lectin from the mushroom Agaricus bisporus (ABL) has the remarkable ability of selectively recognizing the TF-antigen, composed of Galβ1-3GalNAc, Ser/Thr linked to proteins, specifically exposed in neoplastic tissues. Strikingly, the recently solved crystal structure of tetrameric ABL in the presence of TF-antigen and other carbohydrates showed that each monomer has two CRDs, each being able to bind specifically to different monosaccharides that differ only in the configuration of a single hydroxyl, like N-acetyl-d-galactosamine (GalNAc) and N-acetyl-d-glucosamine (GlcNAc). Understanding how lectin CRDs bind and discriminate mono and/or (poly)-saccharides is an important issue in glycobiology, with potential impact in the design of better and selective lectin inhibitors with potential therapeutic properties. In this work, and based on the unusual monosaccharide epimeric specificity of the ABL CRDs, we have performed molecular dynamics simulations of the natural (crystallographic) and inverted (changing GalNAc for GlcNAc and vice-versa) ABL-monosaccharide complexes in order to understand the selective ligand recognition properties of each CRD. We also performed a detailed analysis of the CRD local solvent structure, using previously developed methodology, and related it with the recognition mechanism. Our results provide a detailed picture of each ABL CRD specificity, allowing a better understanding of the carbohydrate selective recognition process in this particular lectin. © 2011 Published by Elsevier Ltd. Fil:Gauto, D.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00086215_v346_n7_p939_Gauto
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Affinity Carbohydrate recognition domain Lectin Molecular dynamics Selectivity Solvent structure Affinity Carbohydrate recognition domain Lectin Selectivity Solvent structure Antigens Carbohydrates Glucose Ligands Molecular dynamics Solvents Tissue Troposphere Crystal structure Agaricus bisporus lectin lectin n acetylgalactosamine unclassified drug Agaricus bisporus article carbohydrate recognition domain complex formation controlled study crystal structure epimer hydrogen bond lectin binding lectin binding site ligand binding molecular dynamics molecular model molecular recognition priority journal protein domain thermodynamics Acetylgalactosamine Acetylglucosamine Agaricus Antigens, Tumor-Associated, Carbohydrate Binding Sites Carbohydrate Conformation Hydrogen Bonding Lectins Molecular Dynamics Simulation Protein Binding Thermodynamics Agaricus bisporus Basidiomycota
spellingShingle	Affinity Carbohydrate recognition domain Lectin Molecular dynamics Selectivity Solvent structure Affinity Carbohydrate recognition domain Lectin Selectivity Solvent structure Antigens Carbohydrates Glucose Ligands Molecular dynamics Solvents Tissue Troposphere Crystal structure Agaricus bisporus lectin lectin n acetylgalactosamine unclassified drug Agaricus bisporus article carbohydrate recognition domain complex formation controlled study crystal structure epimer hydrogen bond lectin binding lectin binding site ligand binding molecular dynamics molecular model molecular recognition priority journal protein domain thermodynamics Acetylgalactosamine Acetylglucosamine Agaricus Antigens, Tumor-Associated, Carbohydrate Binding Sites Carbohydrate Conformation Hydrogen Bonding Lectins Molecular Dynamics Simulation Protein Binding Thermodynamics Agaricus bisporus Basidiomycota Gauto, D.F. Di Lella, S. Estrin, D.A. Monaco, H.L. Martí, M.A. Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
topic_facet	Affinity Carbohydrate recognition domain Lectin Molecular dynamics Selectivity Solvent structure Affinity Carbohydrate recognition domain Lectin Selectivity Solvent structure Antigens Carbohydrates Glucose Ligands Molecular dynamics Solvents Tissue Troposphere Crystal structure Agaricus bisporus lectin lectin n acetylgalactosamine unclassified drug Agaricus bisporus article carbohydrate recognition domain complex formation controlled study crystal structure epimer hydrogen bond lectin binding lectin binding site ligand binding molecular dynamics molecular model molecular recognition priority journal protein domain thermodynamics Acetylgalactosamine Acetylglucosamine Agaricus Antigens, Tumor-Associated, Carbohydrate Binding Sites Carbohydrate Conformation Hydrogen Bonding Lectins Molecular Dynamics Simulation Protein Binding Thermodynamics Agaricus bisporus Basidiomycota
description	Lectins are able to recognize specific carbohydrate structures through their carbohydrate recognition domain (CRD). The lectin from the mushroom Agaricus bisporus (ABL) has the remarkable ability of selectively recognizing the TF-antigen, composed of Galβ1-3GalNAc, Ser/Thr linked to proteins, specifically exposed in neoplastic tissues. Strikingly, the recently solved crystal structure of tetrameric ABL in the presence of TF-antigen and other carbohydrates showed that each monomer has two CRDs, each being able to bind specifically to different monosaccharides that differ only in the configuration of a single hydroxyl, like N-acetyl-d-galactosamine (GalNAc) and N-acetyl-d-glucosamine (GlcNAc). Understanding how lectin CRDs bind and discriminate mono and/or (poly)-saccharides is an important issue in glycobiology, with potential impact in the design of better and selective lectin inhibitors with potential therapeutic properties. In this work, and based on the unusual monosaccharide epimeric specificity of the ABL CRDs, we have performed molecular dynamics simulations of the natural (crystallographic) and inverted (changing GalNAc for GlcNAc and vice-versa) ABL-monosaccharide complexes in order to understand the selective ligand recognition properties of each CRD. We also performed a detailed analysis of the CRD local solvent structure, using previously developed methodology, and related it with the recognition mechanism. Our results provide a detailed picture of each ABL CRD specificity, allowing a better understanding of the carbohydrate selective recognition process in this particular lectin. © 2011 Published by Elsevier Ltd.
format	JOUR
author	Gauto, D.F. Di Lella, S. Estrin, D.A. Monaco, H.L. Martí, M.A.
author_facet	Gauto, D.F. Di Lella, S. Estrin, D.A. Monaco, H.L. Martí, M.A.
author_sort	Gauto, D.F.
title	Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
title_short	Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
title_full	Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
title_fullStr	Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
title_full_unstemmed	Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor
title_sort	structural basis for ligand recognition in a mushroom lectin: solvent structure as specificity predictor
url	http://hdl.handle.net/20.500.12110/paper_00086215_v346_n7_p939_Gauto
work_keys_str_mv	AT gautodf structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT dilellas structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT estrinda structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT monacohl structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT martima structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor
_version_	1807318517865775104

Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor

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