% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Manzoni:859973,
author = {Manzoni, Francesco and Wallerstein, Johan and Schrader,
Tobias E. and Ostermann, Andreas and Coates, Leighton and
Akke, Mikael and Blakeley, Matthew P. and Oksanen, Esko and
Logan, Derek T.},
title = {{E}lucidation of {H}ydrogen {B}onding {P}atterns in
{L}igand-{F}ree, {L}actose- and {G}lycerol-{B}ound
{G}alectin-3{C} by {N}eutron {C}rystallography to {G}uide
{D}rug {D}esign},
journal = {Journal of medicinal chemistry},
volume = {61},
number = {10},
issn = {1520-4804},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2019-00779},
pages = {4412 - 4420},
year = {2018},
abstract = {The medically important drug target galectin-3 binds
galactose-containing moieties on glycoproteins through an
intricate pattern of hydrogen bonds to a largely polar
surface-exposed binding site. All successful inhibitors of
galectin-3 to date have been based on mono- or disaccharide
cores closely resembling natural ligands. A detailed
understanding of the H-bonding networks in these natural
ligands will provide an improved foundation for the design
of novel inhibitors. Neutron crystallography is an ideal
technique to reveal the geometry of hydrogen bonds because
the positions of hydrogen atoms are directly detected rather
than being inferred from the positions of heavier atoms as
in X-ray crystallography. We present three neutron crystal
structures of the C-terminal carbohydrate recognition domain
of galectin-3: the ligand-free form and the complexes with
the natural substrate lactose and with glycerol, which
mimics important interactions made by lactose. The neutron
crystal structures reveal unambiguously the exquisite
fine-tuning of the hydrogen bonding pattern in the binding
site to the natural disaccharide ligand. The ligand-free
structure shows that most of these hydrogen bonds are
preserved even when the polar groups of the ligand are
replaced by water molecules. The protonation states of all
histidine residues in the protein are also revealed and
correlate well with NMR observations. The structures give a
solid starting point for molecular dynamics simulations and
computational estimates of ligand binding affinity that will
inform future drug design.},
cin = {JCNS-FRM-II / Neutronenstreuung ; JCNS-1},
ddc = {610},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106},
pnm = {6G15 - FRM II / MLZ (POF3-6G15) / 6G4 - Jülich Centre for
Neutron Research (JCNS) (POF3-623) / 6215 - Soft Matter,
Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-6G15 / G:(DE-HGF)POF3-6G4 /
G:(DE-HGF)POF3-6215},
experiment = {EXP:(DE-MLZ)BIODIFF-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29672051},
UT = {WOS:000433403600011},
doi = {10.1021/acs.jmedchem.8b00081},
url = {https://juser.fz-juelich.de/record/859973},
}