3c9j

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|PDB= 3c9j |SIZE=350|CAPTION= <scene name='initialview01'>3c9j</scene>, resolution 3.50&Aring;
|PDB= 3c9j |SIZE=350|CAPTION= <scene name='initialview01'>3c9j</scene>, resolution 3.50&Aring;
|SITE= <scene name='pdbsite=AC1:308+Binding+Site+For+Residue+B+101'>AC1</scene>
|SITE= <scene name='pdbsite=AC1:308+Binding+Site+For+Residue+B+101'>AC1</scene>
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|LIGAND= <scene name='pdbligand=308:'>308</scene>
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|LIGAND= <scene name='pdbligand=308:(3S,5S,7S)-TRICYCLO[3.3.1.1~3,7~]DECAN-1-AMINE'>308</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c9j OCA], [http://www.ebi.ac.uk/pdbsum/3c9j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3c9j RCSB]</span>
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[[Category: Salom, D.]]
[[Category: Salom, D.]]
[[Category: Stouffer, A L.]]
[[Category: Stouffer, A L.]]
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[[Category: 308]]
 
[[Category: ion channel]]
[[Category: ion channel]]
[[Category: m2-amantadine complex]]
[[Category: m2-amantadine complex]]
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[[Category: proton channel]]
[[Category: proton channel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:03:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:31:17 2008''

Revision as of 02:31, 31 March 2008


PDB ID 3c9j

Drag the structure with the mouse to rotate
, resolution 3.50Å
Sites:
Ligands:
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



The Crystal structure of Transmembrane domain of M2 protein and Amantadine complex


Overview

The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.

About this Structure

3C9J is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Structural basis for the function and inhibition of an influenza virus proton channel., Stouffer AL, Acharya R, Salom D, Levine AS, Di Costanzo L, Soto CS, Tereshko V, Nanda V, Stayrook S, DeGrado WF, Nature. 2008 Jan 31;451(7178):596-9. PMID:18235504

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