 |
PDBsum entry 4toc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase
|
PDB id
|
|
|
|
4toc
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Concerted motions networking pores and distant ferroxidase centers enable bacterioferritin function and iron traffic.
|
|
|
Authors
|
|
H.Yao,
H.Rui,
R.Kumar,
K.Eshelman,
S.Lovell,
K.P.Battaile,
W.Im,
M.Rivera.
|
|
|
Ref.
|
|
Biochemistry, 2015,
54,
1611-1627.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
X-ray crystallography, molecular dynamics (MD) simulations, and biochemistry
were utilized to investigate the effect of introducing hydrophobic interactions
in the 4-fold (N148L and Q151L) and B-pores (D34F) of Pseudomonas aeruginosa
bacterioferritin B (BfrB) on BfrB function. The structures show only local
structural perturbations and confirm the anticipated hydrophobic interactions.
Surprisingly, structures obtained after soaking crystals in Fe(2+)-containing
crystallization solution revealed that although iron loads into the ferroxidase
centers of the mutants, the side chains of ferroxidase ligands E51 and H130 do
not reorganize to bind the iron ions, as is seen in the wt BfrB structures.
Similar experiments with a double mutant (C89S/K96C) prepared to introduce
changes outside the pores show competent ferroxidase centers that function akin
to those in wt BfrB. MD simulations comparing wt BfrB with the D34F and N148L
mutants show that the mutants exhibit significantly reduced flexibility and
reveal a network of concerted motions linking ferroxidase centers and 4-fold and
B-pores, which are important for imparting ferroxidase centers in BfrB with the
required flexibility to function efficiently. In agreement, the efficiency of
Fe(2+) oxidation and uptake of the 4-fold and B-pore mutants in solution is
significantly compromised relative to wt or C89S/K96C BfrB. Finally, our
structures show a large number of previously unknown iron binding sites in the
interior cavity and B-pores of BfrB, which reveal in unprecedented detail
conduits followed by iron and phosphate ions across the BfrB shell, as well as
paths in the interior cavity that may facilitate nucleation of the iron
phosphate mineral.
|
|
|
|
|
|
|
