 |
PDBsum entry 5e89
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein/inhibitor
|
PDB id
|
|
|
|
5e89
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Sugar binding protein/inhibitor
|
|
|
Title:
|
|
Crystal structure of human galectin-3 crd in complex with 3- fluophenyl-1,2,3-triazolyl thiodigalactoside inhibitor
|
|
Structure:
|
|
Galectin-3. Chain: a. Fragment: unp residues 114-250. Synonym: gal-3,35 kda lectin,carbohydrate-binding protein 35,cbp 35, galactose-specific lectin 3,galactoside-binding protein,galbp,ige- binding protein,l-31,laminin-binding protein,lectin l-29,mac-2 antigen. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: lgals3, mac2. Expressed in: escherichia coli. Expression_system_taxid: 469008.
|
|
Resolution:
|
|
|
1.50Å
|
R-factor:
|
0.169
|
R-free:
|
0.190
|
|
|
Authors:
|
|
P.M.Collins,H.Blanchard
|
|
Key ref:
|
|
T.Delaine
et al.
(2016).
Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.
Chembiochem,
17,
1759-1770.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
13-Oct-15
|
Release date:
|
24-Aug-16
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P17931
(LEG3_HUMAN) -
Galectin-3 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
250 a.a.
137 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Chembiochem
17:1759-1770
(2016)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.
|
|
T.Delaine,
P.Collins,
A.MacKinnon,
G.Sharma,
J.Stegmayr,
V.K.Rajput,
S.Mandal,
I.Cumpstey,
A.Larumbe,
B.A.Salameh,
B.Kahl-Knutsson,
H.van Hattum,
M.van Scherpenzeel,
R.J.Pieters,
T.Sethi,
H.Schambye,
S.Oredsson,
H.Leffler,
H.Blanchard,
U.J.Nilsson.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung
fibrosis in a murine model and that block intracellular galectin-3 accumulation
at damaged vesicles, hence revealing galectin-3-glycan interactions involved in
fibrosis progression and in intracellular galectin-3 activities, is reported.
3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated
as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and
-8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying
low-nanomolar affinities for galectins-1 and -3 were identified in a competitive
fluorescence anisotropy assay. X-ray structural analysis of selected compounds
in complex with galectin-3, together with galectin-3 mutant binding experiments,
revealed that both the aryltriazolyl moieties and fluoro substituents on the
compounds are involved in key interactions responsible for exceptional
affinities towards galectin-3. The most potent galectin-3 antagonist was
demonstrated to act in an assay monitoring galectin-3 accumulation upon
amitriptyline-induced vesicle damage, visualizing a biochemically/medically
relevant intracellular lectin-carbohydrate binding event and that it can be
blocked by a small molecule. The same antagonist administered intratracheally
attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a
dose/response profile comparing favorably with that of oral administration of
the marketed antifibrotic compound pirfenidone.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
