A Density Functional Theory Study of the Iron-Binding Site of Human Serum Transferrin

2004 ◽  
Vol 57 (12) ◽  
pp. 1219 ◽  
Author(s):  
David Rinaldo ◽  
Martin J. Field
Keyword(s):  
Human Serum ◽  
Binding Site ◽  
Conformational Changes ◽  
Metal Binding ◽  
Density Functional ◽  
Release Mechanism ◽  
Serum Transferrin ◽  
Iron Binding ◽  
Iron Release ◽  
Human Serum Transferrin

Human serum transferrin binds ferric ions with high affinity in the blood stream and releases them into cells by a process involving receptor-mediated endocytosis and a decrease in pH. The iron-release mechanism is unclear but protonation events and conformational changes are known to be important. In this study, we investigate properties of the iron-binding site theoretically. Our results suggest that an equatorial histidine could be in its histidinate form when bound to iron at neutral and high pH and that protonation of an axial tyrosine is a key event in iron release. Support for this mechanism from other metal-binding enzymes is also presented.

scholarly journals Density Functional Theory Study on Metal-Binding Energies for Human Serum Transferrin-Metal Complexes

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Tetsuya Sakajiri ◽  
Hirofumi Yajima ◽  
Takaki Yamamura
Keyword(s):  
Density Functional Theory ◽  
Human Serum ◽  
Metal Binding ◽  
Density Functional ◽  
Conformational Transition ◽  
Binding Energies ◽  
Serum Transferrin ◽  
Functional Theory ◽  
Human Serum Transferrin ◽  
Solvation Energies

The absolute values of the metal-binding energies of human serum transferrin (Tf) N-lobe, |ΔE|, were calculated using the density functional theory and were found to increase in magnitude in the following order: Fe(III)>Ga(III)>Al(III)>Cu(II)>Zn(II)>Ni(II). The calculated energies were well correlated with the logarithmic values of the reported metal-binding constants of Tf, which had been experimentally determined, with a correlation coefficient of 0.96. In the estimation of the binding energies, the solvation energies (solvent effect) of free metal ions were a very important factor. The results provide a theoretical explanation for the binding of Fe(III) to Tf, which produces sufficient energy to induce a conformational transition of the Tf molecule, making it possible to interact with Tf receptor 1.

Tertiary structural changes and iron release from human serum transferrin

1997 ◽  
Vol 270 (5) ◽  
pp. 739-750 ◽  
Author(s):  
Sandra L Mecklenburg ◽  
Robert J Donohoe ◽  
Glenn A Olah
Keyword(s):  
Human Serum ◽  
Structural Changes ◽  
Serum Transferrin ◽  
Iron Release ◽  
Human Serum Transferrin

Mutational Analysis of C-Lobe Ligands of Human Serum Transferrin:  Insights into the Mechanism of Iron Release†

Biochemistry ◽  
2005 ◽  
Vol 44 (22) ◽  
pp. 8013-8021 ◽  
Author(s):  
Anne B. Mason ◽  
Peter J. Halbrooks ◽  
Nicholas G. James ◽  
Susan A. Connolly ◽  
Julia R. Larouche ◽  
...  
Keyword(s):  
Human Serum ◽  
Mutational Analysis ◽  
Serum Transferrin ◽  
Iron Release ◽  
Human Serum Transferrin

scholarly journals The Position of Arginine 124 Controls the Rate of Iron Release from the N-lobe of Human Serum Transferrin

2002 ◽  
Vol 278 (8) ◽  
pp. 6027-6033 ◽  
Author(s):  
Ty E. Adams ◽  
Anne B. Mason ◽  
Qing-Yu He ◽  
Peter J. Halbrooks ◽  
Sara K. Briggs ◽  
...  
Keyword(s):  
Human Serum ◽  
Serum Transferrin ◽  
Iron Release ◽  
Human Serum Transferrin

The glycation site specificity of human serum transferrin is a determinant for transferrin's functional impairment under elevated glycaemic conditions

2014 ◽  
Vol 461 (1) ◽  
pp. 33-42 ◽  
Author(s):  
André M. N. Silva ◽  
Paulo R. H. Sousa ◽  
João T. S. Coimbra ◽  
Natércia F. Brás ◽  
Rui Vitorino ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Amino Acid ◽  
Human Serum ◽  
Serum Transferrin ◽  
Site Specificity ◽  
Iron Binding ◽  
Amino Acid Residues ◽  
Human Serum Transferrin ◽  
Structural Alterations ◽  
Iron Binding Protein

Human serum transferrin is susceptible to modification under elevated glycaemic conditions, such as those encountered in diabetes mellitus. The study of transferrin glycation shows that key amino acid residues undergo glycation, inducing structural alterations that compromise its function as an iron-binding protein.

Investigation of the Mechanism of Iron Release from the C-Lobe of Human Serum Transferrin:  Mutational Analysis of the Role of a pH Sensitive Triad†

Biochemistry ◽  
2003 ◽  
Vol 42 (13) ◽  
pp. 3701-3707 ◽  
Author(s):  
Peter J. Halbrooks ◽  
Qing-Yu He ◽  
Sara K. Briggs ◽  
Stephen J. Everse ◽  
Valerie C. Smith ◽  
...  
Keyword(s):  
Human Serum ◽  
Mutational Analysis ◽  
Ph Sensitive ◽  
Serum Transferrin ◽  
Iron Release ◽  
Human Serum Transferrin

scholarly journals Ionic Residues of Human Serum Transferrin Affect Binding to the Transferrin Receptor and Iron Release

Biochemistry ◽  
2012 ◽  
Vol 51 (2) ◽  
pp. 686-694 ◽  
Author(s):  
Ashley N. Steere ◽  
Brendan F. Miller ◽  
Samantha E. Roberts ◽  
Shaina L. Byrne ◽  
N. Dennis Chasteen ◽  
...  
Keyword(s):  
Human Serum ◽  
Transferrin Receptor ◽  
Serum Transferrin ◽  
Iron Release ◽  
Human Serum Transferrin
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