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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Detalles Bibliográficos
Autores principales: Guardia, Carlos Manuel Alberto, Gauto, Diego Fernando, Martí, Marcelo Adrián, Estrin, Dario Ariel
Publicado: 2011
Materias:
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
Aporte de:
id paper:paper_15499596_v51_n8_p1918_Guardia
record_format dspace
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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