The glycosaminoglycans (abbreviated to as: GAGs) comprise a family
of complex anionic polysaccharides including heparin, heparan sulfate,
chondroitin sulphate, dermatan sulfate, keratan sulphate and hyaluronic acid.
In addition to their participation in the physicochemical properties
of the extracellular matrix, glycosaminoglycan fragments are
specifically recognized by protein receptors and they play a role
in the regulation of many processes, such as hemostasis, growth factor control,
anticoagulation and cell adhesion (1-3).
Due to difficulty of obtaining crystals of complexes between protein and glycosaminoglycans,
a limited number of structures are available in the Protein Data Bank.
Several proteins have been co-crystallized with heparin oligosaccharides.
Most of them are of animal origin with the exception of one bacterial enzyme
and two viral proteins. Enzymes are limited to only two viral proteins.
Enzymes are limited to only two cases: one heparinase and one sulfotransferases
illustrating that a large number of protein interacting with heparin sulfate are receptors.
Upon reaching the search page from Glyco-3D, two buttons to query the data base
appear on the left hand panel: Simple search and Advanced Search.
The classification of the GAG-binding proteins is made based on their biological function:
chemokine, complement protein, extra cellular matrix (ECM) protein,
enzyme, growth Factor, lectin, toxin and virus.
Upon selecting one family, a right click opens a new menu
that prompts the user to choose among a sub-classification.
A further right click opens a window on “GAG information”.
Under the name “Select Criteria” search box offers to select among the following items:
nature of GAG
A search box is provided in which appears a drop-down button enlisting
all the entries corresponding to the selected item. The result is prompt
to guide the user in selecting the “hits” found in the data base,
by a simple search engine.
More complex search can be made by combining up criteria
which can be combined from up to four search boxes. A preview of the results
is displayed in an accordion fashion, whereby the classification, the protein name,
the GAG type, and the size of the oligosaccharide are given.
The amount of information provided allows the user to make
an informed choice prior going to “GAG Information”.
The detailed results are available under two tabs: “GAG Information” and “Display and Download”.
Under the button: “GAG Information” is given: protein, classification,
GAG type, species, PDB code, resolution, and length of oligosaccharide,
comments and reference. Provision is also given to view an image
of the source of the protein, along with a graphical representation
of the three-dimensional structure.
Links to Medline (http://www.ncbi.nlm.nih.gov/pubmed/),
Protein Data Base (http://www.rcsb.org/pdb)
and Swissprot (http://www.uniprot.org/uniprot)
are also provided.
Display and Download
On this page, is represented a still three-dimensional ribbon type representation
of the three-dimensional structure which has been constructed
from the reported atomic coordinates with the help of the PyMol molecular visualisation system.
In the case of protein - GAG crystalline complexes, a particular emphasis
is given to indicate the location and conformation of the bound carbohydrate.
The three-dimensional structure can be displayed under Jmol applet windows
that enable basic viewing and measurements options.
The atomic coordinates at the PDB can be downloaded for further use.