3BKD

High resolution Crystal structure of Transmembrane domain of M2 protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for the function and inhibition of an influenza virus proton channel

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.

(2008) Nature 451: 596-599

  • DOI: https://doi.org/10.1038/nature06528
  • Primary Citation of Related Structures:  
    3BKD, 3C9J

  • 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.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transmembrane Domain of Matrix protein M2
A, B, C, D, E
A, B, C, D, E, F, G, H
26N/AMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for Q9Q0P0 (Influenza A virus)
Explore Q9Q0P0 
Go to UniProtKB:  Q9Q0P0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Q0P0
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BOG
Query on BOG

Download Ideal Coordinates CCD File 
I [auth A]
M [auth B]
P [auth C]
Q [auth E]
U [auth G]
I [auth A],
M [auth B],
P [auth C],
Q [auth E],
U [auth G],
V [auth G]
octyl beta-D-glucopyranoside
C14 H28 O6
HEGSGKPQLMEBJL-RKQHYHRCSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
K [auth A]
L [auth A]
N [auth B]
O [auth B]
S [auth E]
K [auth A],
L [auth A],
N [auth B],
O [auth B],
S [auth E],
T [auth E]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
J [auth A],
R [auth E]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B, C, D, E
A, B, C, D, E, F, G, H
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.753α = 90
b = 56.557β = 103.53
c = 56.009γ = 90
Software Package:
Software NamePurpose
CBASSdata collection
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-01-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary