1l7h: Difference between revisions
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[[Image:1l7h.gif|left|200px]] | [[Image:1l7h.gif|left|200px]] | ||
'''Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812''' | {{Structure | ||
|PDB= 1l7h |SIZE=350|CAPTION= <scene name='initialview01'>1l7h</scene>, resolution 1.85Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=BCZ:3-(1-ACETYLAMINO-2-ETHYL-BUTYL)-4-GUANIDINO-2-HYDROXY-CYCLOPENTANECARBOXYLIC+ACID'>BCZ</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [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] | |||
|GENE= | |||
}} | |||
'''Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1L7H is a [ | 1L7H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L7H OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12014958 12014958] | ||
[[Category: Exo-alpha-sialidase]] | [[Category: Exo-alpha-sialidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: r292k mutant]] | [[Category: r292k mutant]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:27:25 2008'' | ||
Revision as of 13:27, 20 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | Exo-alpha-sialidase, with EC number 3.2.1.18 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of R292K mutant influenza virus neuraminidase in complex with BCX-1812
OverviewOverview
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 StructureAbout this Structure
1L7H is a Single protein structure of sequence from Unidentified influenza virus. Full crystallographic information is available from OCA.
ReferenceReference
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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