Structural aspects of binding of alpha-linked digalactosides to human galectin-1

15 páginas, 7 figuras

Detalles Bibliográficos
Autores: Miller, Michelle C., Ribeiro, João P., Roldós, Virginia, Martín-Santamaría, Sonsoles, Cañada, F. Javier, Nesmelova, Irina V., André, Sabine, Pang, Mabel, Klyosov, Anatole A., Baum, Linda G., Jiménez-Barbero, Jesús, Gabius, Hans-Joachim, Mayo, Kevin H.
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/45218
Acceso en línea:http://hdl.handle.net/10261/45218
Access Level:acceso abierto
Palabra clave:Bovine Heart Galectin-1
Mistletoe Lectin
Ligand-Binding
Cell-surface
Molecular-Dynamics
NMR-Spectroscopy
Animal Lectins
Cross-linking
Force-Field
Solid-Phase
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spelling Structural aspects of binding of alpha-linked digalactosides to human galectin-1Miller, Michelle C.Ribeiro, João P.Roldós, VirginiaMartín-Santamaría, SonsolesCañada, F. JavierNesmelova, Irina V.André, SabinePang, MabelKlyosov, Anatole A.Baum, Linda G.Jiménez-Barbero, JesúsGabius, Hans-JoachimMayo, Kevin H.Bovine Heart Galectin-1Mistletoe LectinLigand-BindingCell-surfaceMolecular-DynamicsNMR-SpectroscopyAnimal LectinsCross-linkingForce-FieldSolid-Phase15 páginas, 7 figurasBy definition, adhesion/growth-regulatory galectins are known for their ability to bind beta-galactosides such as Gal beta(1 -> 4)Glc (lactose). Indications for affinity of human galectin-1 to alpha-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-pi stacking. These issues are resolved by a combination of (15)N-(1)H heteronuclear single quantum coherence (HSQC) chemical shift and saturation transfer difference nuclear magnetic resonance (STD NMR) epitope mappings with docking analysis, using the alpha(1 -> 3/4)-linked digalactosides and also Gal alpha(1 -> 6)Glc (melibiose) as test compounds. The experimental part revealed interaction with the canonical lectin site, and this preferentially via the non-reducing-end galactose moiety. Low-energy conformers appear to be selected without notable distortion, as shown by molecular dynamics simulations. With the alpha(1 -> 4) disaccharide, however, the typical CH-pi interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of alpha-linkage in digalactosides has an impact on maintaining CH-pi interactions and the pattern of hydrogen bonding, explaining preference for the alpha(1 -> 3) linkage. Thus, this lectin is able to accommodate both alpha- and beta-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit.This work was sponsored by research grants from the National Cancer Institute (NIH grant # CA096090) to KHM, the Ministery of Science and Innovation of Spain (CTQ2009-08536) to JJ-B and the EC Seventh Framework Program (FP7/2007-2013) under grant agreement no. 260600 ("GlycoHIT") to JJ-B and H-JG.The authors wish to thank the Minnesota Supercomputing Institute (University of Minnesota) for providing computer resources. NMR instrumentation was provided with funds from the NSF (BIR-961477), the University of Minnesota Medical School and the Minnesota Medical Foundation.Minnesota Supercomputing Institute (University of Minnesota) for providing computer resources. NMR instrumentation was provided with funds from the NSF (BIR-961477), the University of Minnesota Medical School and the Minnesota Medical Foundation.Peer reviewedOxford University Press201220122011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/45218reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#Program (FP7/2007-2013) under grant agreement no. 260600 ("GlycoHIT") to JJ-B and H-JGinfo: eu-repo/grantAgreement/EC/FP7/260600http://dx.doi.org/10.1093/glycob/cwr083info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/452182026-05-22T06:33:51Z
dc.title.none.fl_str_mv Structural aspects of binding of alpha-linked digalactosides to human galectin-1
title Structural aspects of binding of alpha-linked digalactosides to human galectin-1
spellingShingle Structural aspects of binding of alpha-linked digalactosides to human galectin-1
Miller, Michelle C.
Bovine Heart Galectin-1
Mistletoe Lectin
Ligand-Binding
Cell-surface
Molecular-Dynamics
NMR-Spectroscopy
Animal Lectins
Cross-linking
Force-Field
Solid-Phase
title_short Structural aspects of binding of alpha-linked digalactosides to human galectin-1
title_full Structural aspects of binding of alpha-linked digalactosides to human galectin-1
title_fullStr Structural aspects of binding of alpha-linked digalactosides to human galectin-1
title_full_unstemmed Structural aspects of binding of alpha-linked digalactosides to human galectin-1
title_sort Structural aspects of binding of alpha-linked digalactosides to human galectin-1
dc.creator.none.fl_str_mv Miller, Michelle C.
Ribeiro, João P.
Roldós, Virginia
Martín-Santamaría, Sonsoles
Cañada, F. Javier
Nesmelova, Irina V.
André, Sabine
Pang, Mabel
Klyosov, Anatole A.
Baum, Linda G.
Jiménez-Barbero, Jesús
Gabius, Hans-Joachim
Mayo, Kevin H.
author Miller, Michelle C.
author_facet Miller, Michelle C.
Ribeiro, João P.
Roldós, Virginia
Martín-Santamaría, Sonsoles
Cañada, F. Javier
Nesmelova, Irina V.
André, Sabine
Pang, Mabel
Klyosov, Anatole A.
Baum, Linda G.
Jiménez-Barbero, Jesús
Gabius, Hans-Joachim
Mayo, Kevin H.
author_role author
author2 Ribeiro, João P.
Roldós, Virginia
Martín-Santamaría, Sonsoles
Cañada, F. Javier
Nesmelova, Irina V.
André, Sabine
Pang, Mabel
Klyosov, Anatole A.
Baum, Linda G.
Jiménez-Barbero, Jesús
Gabius, Hans-Joachim
Mayo, Kevin H.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bovine Heart Galectin-1
Mistletoe Lectin
Ligand-Binding
Cell-surface
Molecular-Dynamics
NMR-Spectroscopy
Animal Lectins
Cross-linking
Force-Field
Solid-Phase
topic Bovine Heart Galectin-1
Mistletoe Lectin
Ligand-Binding
Cell-surface
Molecular-Dynamics
NMR-Spectroscopy
Animal Lectins
Cross-linking
Force-Field
Solid-Phase
description 15 páginas, 7 figuras
publishDate 2011
dc.date.none.fl_str_mv 2011
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/45218
url http://hdl.handle.net/10261/45218
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
Program (FP7/2007-2013) under grant agreement no. 260600 ("GlycoHIT") to JJ-B and H-JG
info: eu-repo/grantAgreement/EC/FP7/260600
http://dx.doi.org/10.1093/glycob/cwr083
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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