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Avian Influenza Neuraminidase, Tamiflu and Relenza
From Proteopedia
http://www.proteopedia.org/wiki/index.php/Avian_Influenza_Neuraminidase%2C_Tamiflu_and_Relenza
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Influenza [1] is a contagious disease caused by a virus. Influenza A[2] (one of several genera and species of influenza) is the most virulent form infecting humans. Largely by facilitating secondarybacterial pneumonias, influenza kills 500,000 people worldwide annually (including about 36,000 in the USA), mostly during seasonal epidemics each year. Most people killed in the annual influenza epidemics are people whose immune defenses are weak, including the very young and the old. Influenza also kills large numbers of animals and birds, both domestic and wild[3]. The influenza virus includes onlyeight proteins. Sequences of these proteins as obtained from numerous strains are available in the NCBI Influenza Virus Resource. For more about the structure and biology, including references for the points made here, please see Influenza at Wikipedia.
Contents[hide] * 1 Influenza Virus Neuraminidase * 1.1 Neuraminidase Structure and Conserved Amino Acids * 2 Pandemic Influenza* 2.1 Past Influenza Pandemics * 2.2 H1N1 "Swine Flu" Pandemic Threat in 2009 * 2.3 H5N1 "Bird Flu" Pandemic Threat * 3 Prophylaxis and Treatment of Influenza * 3.1 Amantadine and Rimantadine - M2 Proton Channel Inhibitors * 3.2 Tamiflu® (oseltamivir) and Relenza® (zanamivir) * 3.2.1 Resistance to Tamiflu and Relenza * 3.2.2 Tamiflu Binds to N1 by InducedFit * 3.3 Cavity in N1: An Opportunity for Drug Design * 4 Links * 5 Notes and Literature References |
Influenza Virus Neuraminidase

Structure of an influenza virus [4].
The surfaces of influenza viruses include, among other molecules, two glycoproteins named hemagglutinin (H) and neuraminidase (N), coded for by the viral segmented RNA genome. Each of these molecules is required forsuccessful infection and spread in a host animal. The hemagglutinin attaches influenza to sialic acid on the surfaces of cells, enabling them to enter and infect cells. After the virus has replicated, neuraminidase (also called sialidase) removes sialic acid from the cell, enabling the newly assembled virions to be released in order to spread and infect other cells. The hemagglutinin (H) andneuraminidase (N) of influenza A are classified into various numbered serotypes or subtypes, such as H1N1, H2N2, H3N2, H5N1, and so forth[5]. For more about neuraminidase, including references for the points made in this paragraph, please see Influenza at Wikipedia.

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Influenza Neuraminidase N1 (2hu4). |
Neuraminidase Structure and Conserved Amino Acids
* Influenza neuraminidase is ahomotetramer[6] ( restore initial scene).
* Each of the four protein chains in the tetramer has a catalytic site, indicated in this scene by the positions of the bound Tamiflu inhibitors.
* The substrate binding site involves only a single protein chain, being distant from neighboring chains.
* The secondary structure is mostly beta, consisting of several beta sheets with three shortalpha helices (Beta Strands, Alpha Helices).
* The residues contacting the Tamiflu inhibitory substrate analog are highly conserved[7].

* These highly conserved residues include some known to be crucial to binding sialic acid substrate: Arg 118, Arg 292 and Arg 371 bind the carboxylate; Arg 152 interacts with the acetamido substituent; and Glu 276 forms hydrogen bonds with the 8- and9-hydroxyl groups of the substrate. These residues are highlighted here in contact with the sialic acid substrate analog Tamiflu. In this scene, atoms and bonds in Tamiflu and the highlighted residues are colored by element: C, O, N.
Pandemic Influenza
Pandemics occur when localized epidemics spread through large regions of the world.
Past Influenza Pandemics
For the meaning of "H1N1", "H2N2",...
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