1b9s: Difference between revisions

Line 1:

[[Image:1b9s.gif|left|200px]]<br /><applet load="1b9s" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1b9s.gif|left|200px]]<br /><applet load="1b9s" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1b9s, resolution 2.5Å" />

'''NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE'''<br />

==Overview==

The active site of type A or B influenza virus neuraminidase is composed, of 11 conserved residues that directly interact with the substrate, sialic, acid. An aromatic benzene ring has been used to replace the pyranose of, sialic acid in our design of novel neuraminidase inhibitors. A, bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the, N-acetyl group on the sialic acid. The hydroxymethyl groups replace two, active site water molecules, which resulted in the high affinity of the, nanomolar inhibitors. However, these inhibitors have greater potency for, type A influenza virus than for type B influenza virus. To resolve the, differences, we determined the X-ray crystal structure of three benzoic, acid substituted inhibitors bound to the active site of B/Lee/40, neuraminidase. The investigation of a hydrophobic aliphatic group and a, hydrophilic guanidino group on the aromatic inhibitors shows changes in, the interaction with the active site residue Glu275. The results provide, an explanation for the difference in efficacy of these inhibitors against, types A and B viruses, even though the 11 active site residues of the, neuraminidase are conserved.

The active site of type A or B influenza virus neuraminidase is composed of 11 conserved residues that directly interact with the substrate, sialic acid. An aromatic benzene ring has been used to replace the pyranose of sialic acid in our design of novel neuraminidase inhibitors. A bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the N-acetyl group on the sialic acid. The hydroxymethyl groups replace two active site water molecules, which resulted in the high affinity of the nanomolar inhibitors. However, these inhibitors have greater potency for type A influenza virus than for type B influenza virus. To resolve the differences, we determined the X-ray crystal structure of three benzoic acid substituted inhibitors bound to the active site of B/Lee/40 neuraminidase. The investigation of a hydrophobic aliphatic group and a hydrophilic guanidino group on the aromatic inhibitors shows changes in the interaction with the active site residue Glu275. The results provide an explanation for the difference in efficacy of these inhibitors against types A and B viruses, even though the 11 active site residues of the neuraminidase are conserved.

==About this Structure==

1B9S 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 FDI 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] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1B9S OCA].

1B9S 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 <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=FDI:'>FDI</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B9S OCA].

==Reference==

Line 14:

[[Category: Influenza b virus]]

[[Category: Single protein]]

[[Category: Air, G.M.]]

[[Category: Air, G M.]]

[[Category: Atigadda, V.R.]]

[[Category: Atigadda, V R.]]

[[Category: Brouillette, W.J.]]

[[Category: Brouillette, W J.]]

[[Category: Duarte, F.]]

[[Category: Finley, J.B.]]

[[Category: Finley, J B.]]

[[Category: Luo, M.]]

[[Category: Zhao, J.J.]]

[[Category: Zhao, J J.]]

[[Category: CA]]

[[Category: FDI]]

Line 28:

[[Category: sialidase]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:52:59 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1b9s.gif|left|200px]]<br /><applet load="1b9s" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1b9s.gif|left|200px]]<br /><applet load="1b9s" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1b9s, resolution 2.5&Aring;" />
 '''NOVEL AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE MAKE SELECTIVE INTERACTIONS WITH CONSERVED RESIDUES AND WATER MOLECULES IN THE ACTIVE SITE'''<br />
 ==Overview==
-The active site of type A or B influenza virus neuraminidase is composed, of 11 conserved residues that directly interact with the substrate, sialic, acid. An aromatic benzene ring has been used to replace the pyranose of, sialic acid in our design of novel neuraminidase inhibitors. A, bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the, N-acetyl group on the sialic acid. The hydroxymethyl groups replace two, active site water molecules, which resulted in the high affinity of the, nanomolar inhibitors. However, these inhibitors have greater potency for, type A influenza virus than for type B influenza virus. To resolve the, differences, we determined the X-ray crystal structure of three benzoic, acid substituted inhibitors bound to the active site of B/Lee/40, neuraminidase. The investigation of a hydrophobic aliphatic group and a, hydrophilic guanidino group on the aromatic inhibitors shows changes in, the interaction with the active site residue Glu275. The results provide, an explanation for the difference in efficacy of these inhibitors against, types A and B viruses, even though the 11 active site residues of the, neuraminidase are conserved.
+The active site of type A or B influenza virus neuraminidase is composed of 11 conserved residues that directly interact with the substrate, sialic acid. An aromatic benzene ring has been used to replace the pyranose of sialic acid in our design of novel neuraminidase inhibitors. A bis(hydroxymethyl)pyrrolidinone ring was constructed in place of the N-acetyl group on the sialic acid. The hydroxymethyl groups replace two active site water molecules, which resulted in the high affinity of the nanomolar inhibitors. However, these inhibitors have greater potency for type A influenza virus than for type B influenza virus. To resolve the differences, we determined the X-ray crystal structure of three benzoic acid substituted inhibitors bound to the active site of B/Lee/40 neuraminidase. The investigation of a hydrophobic aliphatic group and a hydrophilic guanidino group on the aromatic inhibitors shows changes in the interaction with the active site residue Glu275. The results provide an explanation for the difference in efficacy of these inhibitors against types A and B viruses, even though the 11 active site residues of the neuraminidase are conserved.
 ==About this Structure==
-B9S 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 FDI 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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1B9S OCA].
+B9S 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 <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=FDI:'>FDI</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B9S OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Influenza b virus]]
 [[Category: Single protein]]
-[[Category: Air, G.M.]]
+[[Category: Air, G M.]]
-[[Category: Atigadda, V.R.]]
+[[Category: Atigadda, V R.]]
-[[Category: Brouillette, W.J.]]
+[[Category: Brouillette, W J.]]
 [[Category: Duarte, F.]]
-[[Category: Finley, J.B.]]
+[[Category: Finley, J B.]]
 [[Category: Luo, M.]]
-[[Category: Zhao, J.J.]]
+[[Category: Zhao, J J.]]
 [[Category: CA]]
 [[Category: FDI]]
@@ Line 28: / Line 28: @@
 [[Category: sialidase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 11:29:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:52:59 2008''