1l7f
From Proteopedia
(New page: 200px<br /><applet load="1l7f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l7f, resolution 1.80Å" /> '''Crystal structure of...) |
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| - | [[Image:1l7f.gif|left|200px]]<br /><applet load="1l7f" size=" | + | [[Image:1l7f.gif|left|200px]]<br /><applet load="1l7f" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l7f, resolution 1.80Å" /> | caption="1l7f, resolution 1.80Å" /> | ||
'''Crystal structure of influenza virus neuraminidase in complex with BCX-1812'''<br /> | '''Crystal structure of influenza virus neuraminidase in complex with BCX-1812'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Zanamivir and oseltamivir, specific inhibitors of influenza virus | + | Zanamivir and oseltamivir, specific inhibitors of influenza virus neuraminidase, have significantly different characteristics in resistance studies. In both cases resistance is known to arise through mutations in either the hemagglutinin or neuraminidase surface proteins. A new inhibitor under development by Biocryst Pharmaceuticals, BCX-1812, has both a guanidino group, as in zanamivir, and a bulky hydrophobic group, as in oseltamivir. Using influenza A/NWS/Tern/Australia/G70C/75 (H1N9), neuraminidase variants E119G and R292K have previously been selected by different inhibitors. The sensitivity of these variants to BCX-1812 has now been measured and found in both cases to be intermediate between those of zanamivir and oseltamivir. In addition, the X-ray crystal structures of the complexes of BCX-1812 with the wild type and the two mutant neuraminidases were determined. The ligand is bound in an identical manner in each structure, with a rearrangement of the side chain of E276 from its ligand-free position. A structural explanation of the mechanism of resistance of BCX-1812, relative to zanamivir and oseltamivir in particular, is provided. |
==About this Structure== | ==About this Structure== | ||
| - | 1L7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus] with NAG, CA, BCZ and GOL 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:// | + | 1L7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=BCZ:'>BCZ</scene> and <scene name='pdbligand=GOL:'>GOL</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=1L7F OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Unidentified influenza virus]] | [[Category: Unidentified influenza virus]] | ||
| - | [[Category: Colman, P | + | [[Category: Colman, P M.]] |
| - | [[Category: Fernley, R | + | [[Category: Fernley, R T.]] |
[[Category: McDonald, M.]] | [[Category: McDonald, M.]] | ||
| - | [[Category: McKimm-Breshkin, J | + | [[Category: McKimm-Breshkin, J L.]] |
| - | [[Category: Smith, B | + | [[Category: Smith, B J.]] |
| - | [[Category: Varghese, J | + | [[Category: Varghese, J N.]] |
[[Category: BCZ]] | [[Category: BCZ]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: n9 neuraminidase]] | [[Category: n9 neuraminidase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:42:08 2008'' |
Revision as of 11:42, 21 February 2008
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Crystal structure of influenza virus neuraminidase in complex with BCX-1812
Overview
Zanamivir and oseltamivir, specific inhibitors of influenza virus neuraminidase, have significantly different characteristics in resistance studies. In both cases resistance is known to arise through mutations in either the hemagglutinin or neuraminidase surface proteins. A new inhibitor under development by Biocryst Pharmaceuticals, BCX-1812, has both a guanidino group, as in zanamivir, and a bulky hydrophobic group, as in oseltamivir. Using influenza A/NWS/Tern/Australia/G70C/75 (H1N9), neuraminidase variants E119G and R292K have previously been selected by different inhibitors. The sensitivity of these variants to BCX-1812 has now been measured and found in both cases to be intermediate between those of zanamivir and oseltamivir. In addition, the X-ray crystal structures of the complexes of BCX-1812 with the wild type and the two mutant neuraminidases were determined. The ligand is bound in an identical manner in each structure, with a rearrangement of the side chain of E276 from its ligand-free position. A structural explanation of the mechanism of resistance of BCX-1812, relative to zanamivir and oseltamivir in particular, is provided.
About this Structure
1L7F is a Single protein structure of sequence from Unidentified influenza virus with , , and as ligands. Active as Exo-alpha-sialidase, with EC number 3.2.1.18 Full crystallographic information is available from OCA.
Reference
Structural studies of the resistance of influenza virus neuramindase to inhibitors., Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM, J Med Chem. 2002 May 23;45(11):2207-12. PMID:12014958
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