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

David Rinaldo; Martin J. Field

doi:10.1071/CH04103

RESEARCH ARTICLE

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

David Rinaldo ^A and Martin J. Field ^A ^B

+ Author Affiliations

- Author Affiliations

^A Laboratoire de Dynamique Moléculaire, Institut de Biologie Structurale—Jean-Pierre Ebel, CEA/CNRS/UJF, 38041 Grenoble Cedex 01, France.

^B Corresponding author. Email: mjfield@ibs.fr

Australian Journal of Chemistry 57(12) 1219-1222 https://doi.org/10.1071/CH04103
Submitted: 26 April 2004 Accepted: 6 August 2004 Published: 8 December 2004

Abstract

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.

Acknowledgments

The authors thank the Institut de Biologie Structurale—Jean-Pierre Ebel and the Commissariat à l'Energie Atomique for support of this work and the Centre National pour la Recherche Scientifique for an allocation of computer time.

References

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

Abstract

Acknowledgments

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