INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Comparison of Structural, Dynamical and Protein-Carbohydrate Interaction Properties of Human Galectins
Autor/es:
GUARDIA, CARLOS MANUEL ALBERTO; GAUTO, DIEGO FERNANDO; DI LELLA, SANTIAGO; RABINOVICH, GABRIEL ADRIÁN; MARTÍ, MARCELO ADRIÁN; ESTRIN, DARÍO ARIEL
Lugar:
Montevideo, República Oriental del Uruguay
Reunión:
Conferencia; ISBC Latin America Conference; 2010
Institución organizadora:
International Society for Computational Biology
Resumen:
ObjectivesGalectins constitute a family of multi-functional lectin proteins extensively distributed in a variety of tissues and animal species. They are defined by their specificity for β-galactoside sugars and consensus sequence in the carbohydrate recognition domain(CRD). Although all the galectins have a highly homologous CRD, small differences in their binding specificity have been observed which are functionally relevant. The structural basis for these fine tuning is unknown. In humans 15 different galectin sequences have been detected and only seven of them have been structurally characterized. Furthermore, neither a global comparison nor oneof the individual monosaccharide binding sites across the whole protein family has been performed. To bridge this gap, we have performed a structural-dynamical comparison of all human members of the galectin family using state of the art computer simulationtechniques.MethodsIn this work and staring from the available galectin structures, we have performed molecular dynamics simulations of free and ligand bound galectins (solvated with explicit water molecules) to analyze protein and protein-ligand interaction dynamics.All simulations were performed with AMBER9 program. Essential dynamics (ED) analyses and entropy calculation were also performed for all production MD runs, using covariance matrices of the atomic positions along the desired trajectory.Results Our results show that CRD domains of all human galectins are very similar from the global structural and dynamical viewpoint, but minor differences in the sequence and conformation of key residues involved in carbohydrate recognition are responsible fordifferential ligand affinity and selectivity.ConclusionStarting from a common global fold, the fine tuning of key structural elements allows the human galectin family to fulfil their multiple physiological roles.
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