1a4q: Difference between revisions
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==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== | ||
1A4Q is a | 1A4Q 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 DPC 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, LIA and LIB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A4Q OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
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Revision as of 14:23, 5 November 2007
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INFLUENZA VIRUS B/BEIJING/1/87 NEURAMINIDASE COMPLEXED WITH DIHYDROPYRAN-PHENETHYL-PROPYL-CARBOXAMIDE
OverviewOverview
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 StructureAbout this Structure
1A4Q is a Single protein structure of sequence from Influenza b virus with NAG, CA and DPC as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Structure known Active Sites: CHA, CHB, CLA, CLB, LIA and LIB. Full crystallographic information is available from OCA.
ReferenceReference
Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B., Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R, Colman P, Varghese J, J Med Chem. 1998 Mar 12;41(6):798-807. PMID:9526556
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