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PDBsum entry 1qkc
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Tonb dependent receptor
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PDB id
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1qkc
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter fhua.
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Authors
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A.D.Ferguson,
V.Braun,
H.P.Fiedler,
J.W.Coulton,
K.Diederichs,
W.Welte.
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Ref.
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Protein Sci, 2000,
9,
956-963.
[DOI no: ]
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PubMed id
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Abstract
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One alternative method for drug delivery involves the use of
siderophore-antibiotic conjugates. These compounds represent a specific means by
which potent antimicrobial agents, covalently linked to iron-chelating
siderophores, can be actively transported across the outer membrane of
gram-negative bacteria. These "Trojan Horse" antibiotics may prove useful as an
efficient means to combat multi-drug-resistant bacterial infections. Here we
present the crystallographic structures of the natural siderophore-antibiotic
conjugate albomycin and the siderophore phenylferricrocin, in complex with the
active outer membrane transporter FhuA from Escherichia coli. To our knowledge,
this represents the first structure of an antibiotic bound to its cognate
transporter. Albomycins are broad-host range antibiotics that consist of a
hydroxamate-type iron-chelating siderophore, and an antibiotically active,
thioribosyl pyrimidine moiety. As observed with other hydroxamate-type
siderophores, the three-dimensional structure of albomycin reveals an identical
coordination geometry surrounding the ferric iron atom. Unexpectedly, this
antibiotic assumes two conformational isomers in the binding site of FhuA, an
extended and a compact form. The structural information derived from this study
provides novel insights into the diverse array of antibiotic moieties that can
be linked to the distal portion of iron-chelating siderophores and offers a
structural platform for the rational design of hydroxamate-type
siderophore-antibiotic conjugates.
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Secondary reference #1
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Title
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An internal affinity-Tag for purification and crystallization of the siderophore receptor fhua, Integral outer membrane protein from escherichia coli k-12.
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Authors
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A.D.Ferguson,
J.Breed,
K.Diederichs,
W.Welte,
J.W.Coulton.
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Ref.
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Protein Sci, 1998,
7,
1636-1638.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. Still photograph of FhuA crystal on a STOE image platehotating
anode generator combination. The distance c stal-to-image plate is
59 mm. The detector edge corresponds to 3 3' outermost
reflections are t 3.9 A.
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The above figure is
reproduced from the cited reference
which is an Open Access publication published by the Protein Society
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Secondary reference #2
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Title
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Siderophore-Mediated iron transport: crystal structure of fhua with bound lipopolysaccharide.
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Authors
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A.D.Ferguson,
E.Hofmann,
J.W.Coulton,
K.Diederichs,
W.Welte.
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Ref.
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Science, 1998,
282,
2215-2220.
[DOI no: ]
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PubMed id
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Figure 3.
Fig. 3. Representative section of the electron density map.
Stereoview of the final 3F[obs]-2F[calc] electron density map
(blue) at a resolution of 2.7 Å is contoured at 1.5  , showing
the ferrichrome-iron binding site, including water molecules.
The ferrichrome-iron molecule is shown in yellow, and the iron
atom is indicated as a large red sphere. Select side-chain
residues (Glu98, Gly99, and Gln100 from apex B; Tyr116 from apex
C; Tyr244 and Trp246 from L3; Phe^313 from  7; Phe^391
from 9; and
Phe^702 from 21) and the
two water molecules (Wat151 and Wat154) found in the binding
site are labeled (34) and colored white and red, respectively.
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Figure 4.
Fig. 4. Conformational changes induced upon ferrichrome-iron
binding. Superposition of the  -carbon
coordinates of FhuA and its complex with ferrichrome-iron
illustrating the ligand-induced conformational changes observed
in the cork domain. The cork domains of FhuA and its complex
with ferrichrome-iron are shown in purple and yellow,
respectively. The barrel strands (shown in blue) are represented
as thin lines for clarity of the cork domain. Apices A, B, and C
and Glu19 are labeled (34).
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The above figures are
reproduced from the cited reference
with permission from the AAAs
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