3cl0: Difference between revisions
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===N1 Neuraminidase H274Y + oseltamivir=== | |||
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{{ABSTRACT_PUBMED_18480754}} | |||
==About this Structure== | ==About this Structure== | ||
3CL0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CL0 OCA]. | 3CL0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CL0 OCA]. | ||
==Reference== | |||
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants., Collins PJ, Haire LF, Lin YP, Liu J, Russell RJ, Walker PA, Skehel JJ, Martin SR, Hay AJ, Gamblin SJ, Nature. 2008 Jun 26;453(7199):1258-61. Epub 2008 May 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18480754 18480754] | |||
[[Category: Exo-alpha-sialidase]] | [[Category: Exo-alpha-sialidase]] | ||
[[Category: Influenza a virus]] | [[Category: Influenza a virus]] | ||
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[[Category: Viral protein]] | [[Category: Viral protein]] | ||
[[Category: Virion]] | [[Category: Virion]] | ||
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 9 10:11:02 2008'' | |||
Revision as of 10:11, 9 July 2008
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| 3cl0, resolution 2.20Å () | |||||||
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| Ligands: | , | ||||||
| Activity: | Exo-alpha-sialidase, with EC number 3.2.1.18 | ||||||
| Related: | 3ckz, 3cl2 | ||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
N1 Neuraminidase H274Y + oseltamivirN1 Neuraminidase H274Y + oseltamivir
The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants., Collins PJ, Haire LF, Lin YP, Liu J, Russell RJ, Walker PA, Skehel JJ, Martin SR, Hay AJ, Gamblin SJ, Nature. 2008 Jun 26;453(7199):1258-61. Epub 2008 May 14. PMID:18480754
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this StructureAbout this Structure
3CL0 is a Single protein structure of sequence from Influenza a virus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants., Collins PJ, Haire LF, Lin YP, Liu J, Russell RJ, Walker PA, Skehel JJ, Martin SR, Hay AJ, Gamblin SJ, Nature. 2008 Jun 26;453(7199):1258-61. Epub 2008 May 14. PMID:18480754
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