1a4g: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==Overview== | ||
The first paper in this series (see previous article) described, structure-activity studies of carboxamide analogues of zanamivir binding, to influenza virus sialidase types A and B and showed that inhibitory, activity of these compounds was much greater against influenza A enzyme., To understand the large differences in affinities, a number of, protein-ligand complexes have been investigated using crystallography and, molecular dynamics. The crystallographic studies show that the binding of, ligands containing tertiary amide groups is accompanied by the formation, of an intramolecular planar salt bridge between two amino acid residues in, the active site of the enzyme. It is proposed that the unexpected strong, binding of these inhibitors is a result of the burial of hydrophobic, surface ... | The first paper in this series (see previous article) described, structure-activity studies of carboxamide analogues of zanamivir binding, to influenza virus sialidase types A and B and showed that inhibitory, activity of these compounds was much greater against influenza A enzyme., To understand the large differences in affinities, a number of, protein-ligand complexes have been investigated using crystallography and, molecular dynamics. The crystallographic studies show that the binding of, ligands containing tertiary amide groups is accompanied by the formation, of an intramolecular planar salt bridge between two amino acid residues in, the active site of the enzyme. It is proposed that the unexpected strong, binding of these inhibitors is a result of the burial of hydrophobic, surface area and salt-bridge formation in an environment of low, dielectric. In sialidase from type A virus, binding of the carboxamide, moeity and salt-bridge formation have only a minor effect on the positions, of the surrounding residues, whereas in type B enzyme, significant, distortion of the protein is observed. The results suggest that the, decreased affinity in enzyme from influenza B is directly correlated with, the small changes that occur in the amino acid residue interactions, accompanying ligand binding. Molecular dynamics calculations have shown, that the tendency for salt-bridge formation is greater in influenza A, sialidase than influenza B sialidase and that this tendency is a useful, descriptor for the prediction of inhibitor potency. | ||
==About this Structure== | ==About this Structure== | ||
1A4G is a | 1A4G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_b_virus Influenza b virus] with NAG, CA and ZMR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] Structure known Active Sites: CHA, CHB, CLA, CLB, ZAA and ZAB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A4G OCA]. | ||
==Reference== | ==Reference== | ||
| Line 26: | Line 26: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:28:26 2007'' | ||
