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PDBsum entry 1vfd
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Iron transport
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PDB id
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1vfd
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Contents |
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* Residue conservation analysis
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DOI no:
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Biochemistry
35:14473-14479
(1996)
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PubMed id:
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Mutation of arginine 121 in lactoferrin destabilizes iron binding by disruption of anion binding: crystal structures of R121S and R121E mutants.
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H.R.Faber,
C.J.Baker,
C.L.Day,
J.W.Tweedie,
E.N.Baker.
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ABSTRACT
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A conserved arginine residue helps to form the synergistic anion binding site in
transferrins. To probe the importance of this residue for anion binding and iron
binding, Arg 121 has been mutated to Ser and Glu in N-terminal half-molecule of
human lactoferrin. The two mutants, R121S and R121E, have been expressed,
purified, and crystallized. Their three-dimensional structures have been
determined by X-ray diffraction at 2.3 and 2.5 A resolution, respectively. The
structures were determined by molecular replacement and were refined by
restrained least squares methods to final R values of 0.185 and 0.204. Both
mutants still bind iron but with decreased stability. The crystal structures
show that destabilization of iron binding probably results from disruption of
the anion binding site; mutation of Arg 121 removes one wall of the anion
binding pocket and causes the synergistic carbonate ion to be displaced 0.5 A
from its position in the wild-type protein. In the process it becomes partially
detached from the helix N-terminus that forms the rest of the anion binding site.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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T.Jabeen,
S.Sharma,
N.Singh,
A.Bhushan,
and
T.P.Singh
(2005).
Structure of the zinc-saturated C-terminal lobe of bovine lactoferrin at 2.0 A resolution.
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Acta Crystallogr D Biol Crystallogr,
61,
1107-1115.
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PDB code:
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K.Ikuta,
O.Zak,
and
P.Aisen
(2004).
Recycling, degradation and sensitivity to the synergistic anion of transferrin in the receptor-independent route of iron uptake by human hepatoma (HuH-7) cells.
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Int J Biochem Cell Biol,
36,
340-352.
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S.R.Shouldice,
R.J.Skene,
D.R.Dougan,
D.E.McRee,
L.W.Tari,
and
A.B.Schryvers
(2003).
Presence of ferric hydroxide clusters in mutants of Haemophilus influenzae ferric ion-binding protein A.
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Biochemistry,
42,
11908-11914.
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PDB codes:
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T.E.Adams,
A.B.Mason,
Q.Y.He,
P.J.Halbrooks,
S.K.Briggs,
V.C.Smith,
R.T.MacGillivray,
and
S.J.Everse
(2003).
The position of arginine 124 controls the rate of iron release from the N-lobe of human serum transferrin. A structural study.
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J Biol Chem,
278,
6027-6033.
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PDB codes:
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G.B.Jameson,
B.F.Anderson,
W.A.Breyer,
C.L.Day,
J.W.Tweedie,
and
E.N.Baker
(2002).
Structure of a domain-opened mutant (R121D) of the human lactoferrin N-lobe refined from a merohedrally twinned crystal form.
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Acta Crystallogr D Biol Crystallogr,
58,
955-962.
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PDB code:
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O.Zak,
K.Ikuta,
and
P.Aisen
(2002).
The synergistic anion-binding sites of human transferrin: chemical and physiological effects of site-directed mutagenesis.
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Biochemistry,
41,
7416-7423.
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M.Hirose
(2000).
The structural mechanism for iron uptake and release by transferrins.
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Biosci Biotechnol Biochem,
64,
1328-1336.
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R.T.MacGillivray,
M.C.Bewley,
C.A.Smith,
Q.Y.He,
A.B.Mason,
R.C.Woodworth,
and
E.N.Baker
(2000).
Mutation of the iron ligand His 249 to Glu in the N-lobe of human transferrin abolishes the dilysine "trigger" but does not significantly affect iron release.
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Biochemistry,
39,
1211-1216.
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PDB code:
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K.Mizutani,
H.Yamashita,
H.Kurokawa,
B.Mikami,
and
M.Hirose
(1999).
Alternative structural state of transferrin. The crystallographic analysis of iron-loaded but domain-opened ovotransferrin N-lobe.
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J Biol Chem,
274,
10190-10194.
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PDB codes:
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W.A.Breyer,
R.L.Kingston,
B.F.Anderson,
and
E.N.Baker
(1999).
On the molecular-replacement problem in the presence of merohedral twinning: structure of the N-terminal half-molecule of human lactoferrin.
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Acta Crystallogr D Biol Crystallogr,
55,
129-138.
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X.L.Sun,
H.M.Baker,
S.C.Shewry,
G.B.Jameson,
and
E.N.Baker
(1999).
Structure of recombinant human lactoferrin expressed in Aspergillus awamori.
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Acta Crystallogr D Biol Crystallogr,
55,
403-407.
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PDB code:
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G.B.Jameson,
B.F.Anderson,
G.E.Norris,
D.H.Thomas,
and
E.N.Baker
(1998).
Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change.
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Acta Crystallogr D Biol Crystallogr,
54,
1319-1335.
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PDB code:
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Y.Li,
W.R.Harris,
A.Maxwell,
R.T.MacGillivray,
and
T.Brown
(1998).
Kinetic studies on the removal of iron and aluminum from recombinant and site-directed mutant N-lobe half transferrins.
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Biochemistry,
37,
14157-14166.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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