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PDBsum entry 5dyh
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Metal transport
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PDB id
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5dyh
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References listed in PDB file
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Key reference
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Title
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Unusual synergism of transferrin and citrate in the regulation of ti(IV) speciation, Transport, And toxicity.
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Authors
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A.D.Tinoco,
M.Saxena,
S.Sharma,
N.Noinaj,
Y.Delgado,
E.P.Quiñones gonzález,
S.E.Conklin,
N.Zambrana,
S.A.Loza-Rosas,
T.B.Parks.
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Ref.
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J Am Chem Soc, 2016,
138,
5659-5665.
[DOI no: ]
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PubMed id
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Abstract
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Human serum transferrin (sTf) is a protein that mediates the transport of iron
from blood to cells. Assisted by the synergistic anion carbonate, sTf transports
Fe(III) by binding the metal ion in a closed conformation. Previous studies
suggest sTf's role as a potential transporter of other metals such as titanium.
Ti is a widely used metal in colorants, foods, and implants. A substantial
amount of Ti is leached into blood from these implants. However, the fate of the
leached Ti and its transport into the cells is not known. Understanding Ti
interaction with sTf assumes a greater significance with our ever increasing
exposure to Ti in the form of implants. On the basis of in vitro studies, it was
speculated that transferrin can bind Ti(IV) assisted by a synergistic anion.
However, the role and identity of the synergistic anion(s) and the
conformational state in which sTf binds Ti(IV) are not known. Here we have
solved the first X-ray crystal structure of a Ti(IV)-bound sTf. We find that sTf
binds Ti(IV) in an open conformation with both carbonate and citrate as
synergistic anions at the metal binding sites, an unprecedented role for
citrate. Studies with cell lines suggest that Ti(IV)-sTf is transported into
cells and that sTf and citrate regulate the metal's blood speciation and
attenuate its cytotoxic property. Our results provide the first glimpse into the
citrate-transferrin synergism in the regulation of Ti(IV) bioactivity and offers
insight into the future design of Ti(IV)-based anticancer drugs.
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