3BKD

High resolution Crystal structure of Transmembrane domain of M2 protein

3BKD の概要

• エントリーDOI: 10.2210/pdb3bkd/pdb
• 分子名称: Transmembrane Domain of Matrix protein M2, octyl beta-D-glucopyranoside, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: proton channel, m2tm, influenza a virus m2 protein, viral protein, membrane protein
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 24807.73

構造登録者

Stouffer, A.L.,Acharya, R.,Salom, D. (登録日: 2007-12-06, 公開日: 2008-01-29, 最終更新日: 2024-11-20)

主引用文献

Stouffer, A.L.,Acharya, R.,Salom, D.,Levine, A.S.,Di Costanzo, L.,Soto, C.S.,Tereshko, V.,Nanda, V.,Stayrook, S.,DeGrado, W.F.
Structural basis for the function and inhibition of an influenza virus proton channel
Nature, 451:596-599, 2008

PubMed Abstract: 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.

PubMed: 18235504
DOI: 10.1038/nature06528

実験手法

X-RAY DIFFRACTION (2.05 Å)