B-lactoglobulin's conformational requirements for ligand binding at the calyx and the dimer interphase : a flexible docking study

Simple item page
dc.audience researchers es_MX
dc.contributor.author Lenin Dominguez Ramirez, 0000-0002-3483-4658
dc.contributor.other Del Moral Ramírez, Elizabeth
dc.contributor.other Cortes Hernández, Paulina
dc.contributor.other García Garibay, Mariano, 0000-0002-9132-7126
dc.contributor.other Jiménez Guzmán, Judith
dc.coverage US es_MX
dc.date.accessioned 2018-05-31T00:04:12Z
dc.date.available 2018-05-31T00:04:12Z
dc.date.issued 2013
dc.description β-lactoglobulin (BLG) is an abundant milk protein relevant for industry and biotechnology, due significantly to its ability to bind a wide range of polar and apolar ligands. While hydrophobic ligand sites are known, sites for hydrophilic ligands such as the prevalent milk sugar, lactose, remain undetermined. Through the use of molecular docking we first, analyzed the known fatty acid binding sites in order to dissect their atomistic determinants and second, predicted the interaction sites for lactose with monomeric and dimeric BLG. We validated our approach against BLG structures co-crystallized with ligands and report a computational setup with a reduced number of flexible residues that is able to reproduce experimental results with high precision. Blind dockings with and without flexible side chains on BLG showed that: i) 13 experimentally-determined ligands fit the calyx requiring minimal movement of up to 7 residues out of the 23 that constitute this binding site. ii) Lactose does not bind the calyx despite conformational flexibility, but binds the dimer interface and an alternate Site C. iii) Results point to a probable lactolation site in the BLG dimer interface, at K141, consistent with previous biochemical findings. In contrast, no accessible lysines are found near Site C. iv) lactose forms hydrogen bonds with residues from both monomers stabilizing the dimer through a claw-like structure. Overall, these results improve our understanding of BLG's binding sites, importantly narrowing down the calyx residues that control ligand binding. Moreover, our results emphasize the importance of the dimer interface as an insufficiently explored, biologically relevant binding site of particular importance for hydrophilic ligands. Furthermore our analyses suggest that BLG is a robust scaffold for multiple ligand-binding, suitable for protein design, and advance our molecular understanding of its ligand sites to a point that allows manipulation to control binding. es_MX
dc.format application/pdf es_MX
dc.identificador.materia 2 es_MX
dc.identifier.other https://doi.org/10.1371/journal.pone.0079530
dc.identifier.uri http://hdl.handle.net/20.500.12222/42
dc.language eng es_MX
dc.publisher Public Library of Science es_MX
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights.license info:eu-repo/semantics/openAccess es_MX
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ es_MX
dc.source.other PLOS ONE (11) vol.8 (2013) es_MX
dc.source.other ISSN: 1932-6203 es_MX
dc.subject BIOLOGÍA Y QUÍMICA es_MX
dc.subject.keywords Calix es_MX
dc.subject.keywords Lactose es_MX
dc.subject.keywords Lysine es_MX
dc.subject.keywords Milk es_MX
dc.subject.keywords Vitamins es_MX
dc.subject.keywords Dimers es_MX
dc.subject.keywords Fatty Acids es_MX
dc.subject.keywords Binding Analysis es_MX
dc.title B-lactoglobulin's conformational requirements for ligand binding at the calyx and the dimer interphase : a flexible docking study es_MX
dc.type article es_MX
dc.type.version info:eu-repo/semantics/publishedVersion es_MX
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
000032.PDF
Size:
2.66 MB
Format:
Adobe Portable Document Format
Description:
13 páginas
Download
No Thumbnail Available
Name:
000032.xml
Size:
3.68 MB
Format:
Extensible Markup Language
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Artículos Científicos