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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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v346_n7_p939_Gauto http://hdl.handle.net/20.500.12110/paper_00086215_v346_n7_p939_Gauto |
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paper:paper_00086215_v346_n7_p939_Gauto2023-06-08T14:33:00Z Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor Gauto, Diego Fernando Estrin, Dario Ariel Martí, Marcelo Adrián 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. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v346_n7_p939_Gauto 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, Diego Fernando Estrin, Dario Ariel Martí, Marcelo Adrián 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. |
| author |
Gauto, Diego Fernando Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_facet |
Gauto, Diego Fernando Estrin, Dario Ariel Martí, Marcelo Adrián |
| author_sort |
Gauto, Diego Fernando |
| 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 |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v346_n7_p939_Gauto http://hdl.handle.net/20.500.12110/paper_00086215_v346_n7_p939_Gauto |
| work_keys_str_mv |
AT gautodiegofernando structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT estrindarioariel structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor AT martimarceloadrian structuralbasisforligandrecognitioninamushroomlectinsolventstructureasspecificitypredictor |
| _version_ |
1768543733082488832 |