Name
Title | ||
|---|---|---|
Computational studies on the interaction of ABO-active saccharides with the norovirus VA387 capsid protein can explain experimental binding data. |
Abstract | ||
|---|---|---|
Norovirus strains are known to cause recurring epidemics of winter vomiting disease. The crystal structure of the capsid protein
of VA387, a representative of the clinically important GII.4 genocluster, was recently solved in complex with histo-blood
group A- and B-trisaccharides. However, the VA387 strain is known to bind also to other natural carbohydrates for which detailed
structural information of the complexes is not available. In this study we have computationally explored the fit of the VA387
with a set of naturally occurring carbohydrate ligands containing a terminal α1,2-linked fucose. MD simulations both with
explicit and implicit solvent models indicate that type 1 and 3 extensions of the ABO-determinant including ALeb and BLeb pentasaccharides can be well accommodated in the site. Scoring with Glide XP indicates that the downstream extensions of
the ABO-determinants give an increase in binding strength, although the α1,2-linked fucose is the single strongest interacting
residue. An error was discovered in the geometry of the GalNAc-Gal moiety of the published crystal structure of the A-trisaccharide/VA387
complex. The present modeling of the complexes with histo-blood group A-active structures shows some contacts which provide
insight into mutational data, explaining the involvement of I389 and Q331. Our results can be applicable in structure-based
design of adhesion inhibitors of noroviruses. |
Year | DOI | Venue |
|---|---|---|
2010 | 10.1007/s10822-010-9353-5 | Journal of computer-aided molecular design |
Keywords | Field | DocType |
Norovirus,Blood group determinants,ABO-saccharides,Molecular docking,Molecular dynamics | Docking (molecular),Plasma protein binding,Binding site,Fucose,Docking (dog),Biochemistry,Computational chemistry,Chemistry,Capsid,Molecular dynamics,Solvent models,Stereochemistry | Journal |
Volume | Issue | ISSN |
24 | 5 | 1573-4951 |
Citations | PageRank | References |
0 | 0.34 | 5 |
Authors | ||
6 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Chaitanya A. K. Koppisetty | 1 | 2 | 1.41 |
| Waqas Nasir | 2 | 0 | 0.34 |
| Francesco Strino | 3 | 2 | 1.79 |
| Gustaf E. Rydell | 4 | 0 | 0.34 |
| Göran Larson | 5 | 0 | 0.34 |
| Per-Georg Nyholm | 6 | 4 | 1.84 |