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Anion-mediated Fe3+ Release Mechanism in Ovotransferrin C-lobe

IR@CSIR-CFTRI

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Relation http://ir.cftri.com/1624/
JBC-12-01
 
Title Anion-mediated Fe3+ Release Mechanism in Ovotransferrin C-lobe
 
Creator Kimihiko, Mizutani
Muralidhara, B. K.
Honami, Yamashita
Satoshi, Tabata
 
Subject 29 Protein Chemistry
03 Proteins
 
Description The differential properties of anion-mediated Fe3_ release
between the N- and C-lobes of transferrins have
been a focus in transferrin biochemistry. The structural
and kinetic characteristics for isolated lobe have, however,been documented with the N-lobe only. Here we
demonstrate for the first time the quantitative Fe3_ release kinetics and the anion-binding structure for the
isolated C-lobe of ovotransferrin. In the presence of pyrophosphate, sulfate, and nitrilotriacetate anions, the
C-lobe released Fe3_ with a decelerated rate in a single
exponential progress curve, and the observed first order
rate constants displayed a hyperbolic profile as a function
of the anion concentration. The profile was consistent
with a newly derived single-pathway Fe3_ release
model in which the holo form is converted depending on
the anion concentration into a “mixed ligand” intermediate
that releases Fe3_. The apo C-lobe was crystallized
in ammonium sulfate solution, and the structure determined
at 2.3 Å resolution demonstrated the existence of
a single bound SO4 2_ in the interdomain cleft, which
interacts directly with Thr461-OG1, Tyr431-OH, and
His592-NE2 and indirectly with Tyr524-OH. The latter
three groups are Fe3_-coordinating ligands, strongly
suggesting the facilitated Fe3_ release upon the anion
occupation at this site. The SO4 2_ binding structure supported the single-pathway kinetic model.
 
Date 2001-09
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/1624/1/JBC_276_35940_-_35946_2001_NA.pdf
Kimihiko, Mizutani and Muralidhara, B. K. and Honami, Yamashita and Satoshi, Tabata (2001) Anion-mediated Fe3+ Release Mechanism in Ovotransferrin C-lobe. Journal of Biological Chemistry, 276 (28). pp. 35940-35946.