NS5B: Difference between revisions

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'''Figure 5''' shows much of the x-ray crystallography work that has gone into NS5B to date. Each of the forty three structures included in the superposition contain at least one ligand, the ligands range from ions and small molecules to nucleotides and non-nucleoside analogue inhibitors. Positioning the structure in the familiar orientation with the <scene name='NS5B/Ns5b_with_ligands/3'>domains</scene> colored as above, it is obvious that there are two primary areas where ligands are clustering. Several nucleotides, oligonucleotides and non-nucleoside analogue inhibitors can be found in the area right around the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene>. There is another site that is about 30-35Å from the active site, an <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene>, where again ligands are clustering. There is a rGTP binding site here that seems to activate the enzyme and a nearby site where inhibitors bind and disrupt the activity of the enzyme.

The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene> are thought to work by disrupting the ''primer grip'' site causing an inability of the enzyme to efficiently hold and extend a growing primer strand. The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene> work through a poorly understood mechanism, several explanations for their ability to inhibit the enzyme have been proposed. The ~~common propositions~~ are that the

The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene> are thought to work by disrupting the ''primer grip'' site causing an inability of the enzyme to efficiently hold and extend a growing primer strand. The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene> work through a poorly understood mechanism, several explanations for their ability to inhibit the enzyme have been proposed. The commonly proposed explanations are that these inhibitors lock the enzyme in an inactive conformation, inhibit binding of the rGTP that binds in the area and has been shown to stimulate activity, or that this interface is critical in protein-protein interactions and disruption of these interactions by the inhibitors disrupts an oligomerization of several NS5B protomers thus making each less efficient.

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@@ Line 30: / Line 30: @@
 '''Figure 5''' shows much of the x-ray crystallography work that has gone into NS5B to date. Each of the forty three structures included in the superposition contain at least one ligand, the ligands range from ions and small molecules to nucleotides and non-nucleoside analogue inhibitors. Positioning the structure in the familiar orientation with the <scene name='NS5B/Ns5b_with_ligands/3'>domains</scene> colored as above, it is obvious that there are two primary areas where ligands are clustering. Several nucleotides, oligonucleotides and non-nucleoside analogue inhibitors can be found in the area right around the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene>. There is another site that is about 30-35Å from the active site, an <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene>, where again ligands are clustering. There is a rGTP binding site here that seems to activate the enzyme and a nearby site where inhibitors bind and disrupt the activity of the enzyme.
-The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene> are thought to work by disrupting the ''primer grip'' site causing an inability of the enzyme to efficiently hold and extend a growing primer strand. The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene> work through a poorly understood mechanism, several explanations for their ability to inhibit the enzyme have been proposed. The common propositions are that the
+The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/4'>active site</scene> are thought to work by disrupting the ''primer grip'' site causing an inability of the enzyme to efficiently hold and extend a growing primer strand. The inhibitors that bind near the <scene name='NS5B/Ns5b_with_ligands/5'>allosteric site</scene> work through a poorly understood mechanism, several explanations for their ability to inhibit the enzyme have been proposed. The commonly proposed explanations are that these inhibitors lock the enzyme in an inactive conformation, inhibit binding of the rGTP that binds in the area and has been shown to stimulate activity, or that this interface is critical in protein-protein interactions and disruption of these interactions by the inhibitors disrupts an oligomerization of several NS5B protomers thus making each less efficient.
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