 |
PDBsum entry 1wp1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein
|
PDB id
|
|
|
|
1wp1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of the drug discharge outer membrane protein, Oprm, Of pseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end.
|
|
|
Authors
|
|
H.Akama,
M.Kanemaki,
M.Yoshimura,
T.Tsukihara,
T.Kashiwagi,
H.Yoneyama,
S.Narita,
A.Nakagawa,
T.Nakae.
|
|
|
Ref.
|
|
J Biol Chem, 2004,
279,
52816-52819.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The OprM lipoprotein of Pseudomonas aeruginosa is a member of the MexAB-OprM
xenobiotic-antibiotic transporter subunits that is assumed to serve as the drug
discharge duct across the outer membrane. The channel structure must differ from
that of the porin-type open pore because the protein facilitates the exit of
antibiotics but not the entry. For better understanding of the
structure-function linkage of this important pump subunit, we studied the x-ray
crystallographic structure of OprM at the 2.56-angstroms resolution. The overall
structure exhibited trimeric assembly of the OprM monomer that consisted mainly
of two domains: the membrane-anchoring beta-barrel and the cavity-forming
alpha-barrel. OprM anchors the outer membrane by two modes of membrane
insertions. One is via the covalently attached NH(2)-terminal fatty acids and
the other is the beta-barrel structure consensus on the outer membrane-spanning
proteins. The beta-barrel had a pore opening with a diameter of about 6-8
angstroms, which is not large enough to accommodate the exit of any antibiotics.
The periplasmic alpha-barrel was about 100 angstroms long formed mainly by a
bundle of alpha-helices that formed a solvent-filled cavity of about 25,000
angstroms(3). The proximal end of the cavity was tightly sealed, thereby not
permitting the entry of any molecule. The result of this structure was that the
resting state of OprM had a small outer membrane pore and a tightly closed
periplasmic end, which sounds plausible because the protein should not allow
free access of antibiotics. However, these observations raised another unsolved
problem about the mechanism of opening of the OprM cavity ends. The crystal
structure offers possible mechanisms of pore opening and pump assembly.
|
|
|
|
|
|
|
|
Figure 2.
FIG. 2. OprM cavity and the cavity ends. A, vertical views
and horizontal slices of the OprM trimer. Three monomers are
colored blue, red, and green. The left figure shows a vertical
view of the OprM trimer. The right figures exhibited horizontal
slices of the OprM trimer at the  -barrel, equator, and
the periplasmic end. Approximate pore diameters are shown. B,
periplasmic end of the OprM trimer. Triplet Leu412 residues are
shown by the space-filling model (yellow). The remaining amino
acid residues are shown by a stick model.
|
|
Figure 4.
FIG. 4. Stereoscopic view of the OprM-MexB junction. Side
view of the OprM-MexB junction in the trimeric form was shown.
Arrays of hydrophobic amino acids, Val198-Gly199-Val200 of OprM
(red, magenta, and yellow) and that of Ala^736-Leu737-Gly738 of
MexB (blue, cyan, and white) were shown by the space-filling
model.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
52816-52819)
copyright 2004.
|
|
|
|
|
|
|
