An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network
Galectins, a family of evolutionarily conserved animal lectins, have been shown to modulate signaling processes leading to inflammation, apoptosis, immunoregulation, and angiogenesis through their ability to interact with poly-N-acetyllactosamine-enriched glycoconjugates. To date 16 human galectin c...
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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15499596_v51_n8_p1918_Guardia http://hdl.handle.net/20.500.12110/paper_15499596_v51_n8_p1918_Guardia |
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paper:paper_15499596_v51_n8_p1918_Guardia2023-06-08T16:21:22Z An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network Guardia, Carlos Manuel Alberto Gauto, Diego Fernando Martí, Marcelo Adrián Estrin, Dario Ariel Angiogenesis Carbohydrate-recognition domains Classical molecular dynamics Computational analysis Dynamics characteristic Entropy value Galectins Glycoconjugates Immunoregulation Ligand affinity Ligand binding Molecular levels Protein-ligand interactions Sequence analysis Signaling process Specific inhibitors Structural differences Structural information Binding energy Binding sites Carbohydrates Cell death Computational methods Dynamics Glucose Molecular dynamics Proteins Structural analysis Tissue Ligands epitope galectin galectin 12, human galectin 4 LGALS13 protein, human ligand placenta protein poly N acetyllactosamine poly-N-acetyllactosamine polysaccharide amino acid sequence article binding site chemical structure chemistry entropy human immunology metabolism methodology molecular dynamics molecular genetics nuclear magnetic resonance spectroscopy phylogeny physiology protein binding protein database protein tertiary structure sequence homology signal transduction systems biology X ray crystallography Amino Acid Sequence Binding Sites Crystallography, X-Ray Databases, Protein Entropy Epitopes Galectin 4 Galectins Humans Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Dynamics Simulation Molecular Sequence Data Phylogeny Polysaccharides Pregnancy Proteins Protein Binding Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction Systems Biology Galectins, a family of evolutionarily conserved animal lectins, have been shown to modulate signaling processes leading to inflammation, apoptosis, immunoregulation, and angiogenesis through their ability to interact with poly-N-acetyllactosamine-enriched glycoconjugates. To date 16 human galectin carbohydrate recognition domains have been established by sequence analysis and found to be expressed in several tissues. Given the divergent functions of these lectins, it is of vital importance to understand common and differential features in order to search for specific inhibitors of individual members of the human galectin family. In this work we performed an integrated computational analysis of all individual members of the human galectin family. In the first place, we have built homology-based models for galectin-4 and -12 N-terminus, placental protein 13 (PP13) and PP13-like protein for which no experimental structural information is available. We have then performed classical molecular dynamics simulations of the whole 15 members family in free and ligand-bound states to analyze protein and protein-ligand interaction dynamics. Our results show that all galectins adopt the same fold, and the carbohydrate recognition domains are very similar with structural differences located in specific loops. These differences are reflected in the dynamics characteristics, where mobility differences translate into entropy values which significantly influence their ligand affinity. Thus, ligand selectivity appears to be modulated by subtle differences in the monosaccharide binding sites. Taken together, our results may contribute to the understanding, at a molecular level, of the structural and dynamical determinants that distinguish individual human galectins. © 2011 American Chemical Society. Fil:Guardia, C.M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gauto, D.F. 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. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15499596_v51_n8_p1918_Guardia http://hdl.handle.net/20.500.12110/paper_15499596_v51_n8_p1918_Guardia |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Angiogenesis Carbohydrate-recognition domains Classical molecular dynamics Computational analysis Dynamics characteristic Entropy value Galectins Glycoconjugates Immunoregulation Ligand affinity Ligand binding Molecular levels Protein-ligand interactions Sequence analysis Signaling process Specific inhibitors Structural differences Structural information Binding energy Binding sites Carbohydrates Cell death Computational methods Dynamics Glucose Molecular dynamics Proteins Structural analysis Tissue Ligands epitope galectin galectin 12, human galectin 4 LGALS13 protein, human ligand placenta protein poly N acetyllactosamine poly-N-acetyllactosamine polysaccharide amino acid sequence article binding site chemical structure chemistry entropy human immunology metabolism methodology molecular dynamics molecular genetics nuclear magnetic resonance spectroscopy phylogeny physiology protein binding protein database protein tertiary structure sequence homology signal transduction systems biology X ray crystallography Amino Acid Sequence Binding Sites Crystallography, X-Ray Databases, Protein Entropy Epitopes Galectin 4 Galectins Humans Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Dynamics Simulation Molecular Sequence Data Phylogeny Polysaccharides Pregnancy Proteins Protein Binding Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction Systems Biology |
| spellingShingle |
Angiogenesis Carbohydrate-recognition domains Classical molecular dynamics Computational analysis Dynamics characteristic Entropy value Galectins Glycoconjugates Immunoregulation Ligand affinity Ligand binding Molecular levels Protein-ligand interactions Sequence analysis Signaling process Specific inhibitors Structural differences Structural information Binding energy Binding sites Carbohydrates Cell death Computational methods Dynamics Glucose Molecular dynamics Proteins Structural analysis Tissue Ligands epitope galectin galectin 12, human galectin 4 LGALS13 protein, human ligand placenta protein poly N acetyllactosamine poly-N-acetyllactosamine polysaccharide amino acid sequence article binding site chemical structure chemistry entropy human immunology metabolism methodology molecular dynamics molecular genetics nuclear magnetic resonance spectroscopy phylogeny physiology protein binding protein database protein tertiary structure sequence homology signal transduction systems biology X ray crystallography Amino Acid Sequence Binding Sites Crystallography, X-Ray Databases, Protein Entropy Epitopes Galectin 4 Galectins Humans Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Dynamics Simulation Molecular Sequence Data Phylogeny Polysaccharides Pregnancy Proteins Protein Binding Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction Systems Biology Guardia, Carlos Manuel Alberto Gauto, Diego Fernando Martí, Marcelo Adrián Estrin, Dario Ariel An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| topic_facet |
Angiogenesis Carbohydrate-recognition domains Classical molecular dynamics Computational analysis Dynamics characteristic Entropy value Galectins Glycoconjugates Immunoregulation Ligand affinity Ligand binding Molecular levels Protein-ligand interactions Sequence analysis Signaling process Specific inhibitors Structural differences Structural information Binding energy Binding sites Carbohydrates Cell death Computational methods Dynamics Glucose Molecular dynamics Proteins Structural analysis Tissue Ligands epitope galectin galectin 12, human galectin 4 LGALS13 protein, human ligand placenta protein poly N acetyllactosamine poly-N-acetyllactosamine polysaccharide amino acid sequence article binding site chemical structure chemistry entropy human immunology metabolism methodology molecular dynamics molecular genetics nuclear magnetic resonance spectroscopy phylogeny physiology protein binding protein database protein tertiary structure sequence homology signal transduction systems biology X ray crystallography Amino Acid Sequence Binding Sites Crystallography, X-Ray Databases, Protein Entropy Epitopes Galectin 4 Galectins Humans Ligands Magnetic Resonance Spectroscopy Models, Molecular Molecular Dynamics Simulation Molecular Sequence Data Phylogeny Polysaccharides Pregnancy Proteins Protein Binding Protein Structure, Tertiary Sequence Homology, Amino Acid Signal Transduction Systems Biology |
| description |
Galectins, a family of evolutionarily conserved animal lectins, have been shown to modulate signaling processes leading to inflammation, apoptosis, immunoregulation, and angiogenesis through their ability to interact with poly-N-acetyllactosamine-enriched glycoconjugates. To date 16 human galectin carbohydrate recognition domains have been established by sequence analysis and found to be expressed in several tissues. Given the divergent functions of these lectins, it is of vital importance to understand common and differential features in order to search for specific inhibitors of individual members of the human galectin family. In this work we performed an integrated computational analysis of all individual members of the human galectin family. In the first place, we have built homology-based models for galectin-4 and -12 N-terminus, placental protein 13 (PP13) and PP13-like protein for which no experimental structural information is available. We have then performed classical molecular dynamics simulations of the whole 15 members family in free and ligand-bound states to analyze protein and protein-ligand interaction dynamics. Our results show that all galectins adopt the same fold, and the carbohydrate recognition domains are very similar with structural differences located in specific loops. These differences are reflected in the dynamics characteristics, where mobility differences translate into entropy values which significantly influence their ligand affinity. Thus, ligand selectivity appears to be modulated by subtle differences in the monosaccharide binding sites. Taken together, our results may contribute to the understanding, at a molecular level, of the structural and dynamical determinants that distinguish individual human galectins. © 2011 American Chemical Society. |
| author |
Guardia, Carlos Manuel Alberto Gauto, Diego Fernando Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Guardia, Carlos Manuel Alberto Gauto, Diego Fernando Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Guardia, Carlos Manuel Alberto |
| title |
An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| title_short |
An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| title_full |
An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| title_fullStr |
An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| title_full_unstemmed |
An integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| title_sort |
integrated computational analysis of the structure, dynamics, and ligand binding interactions of the human galectin network |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15499596_v51_n8_p1918_Guardia http://hdl.handle.net/20.500.12110/paper_15499596_v51_n8_p1918_Guardia |
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