Standard Article

Genetic Engineering of Hemoglobin

Biotechnology

  1. Jeremy Tame

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200300156

Reviews in Cell Biology and Molecular Medicine

Reviews in Cell Biology and Molecular Medicine

How to Cite

Tame, J. 2006. Genetic Engineering of Hemoglobin. Reviews in Cell Biology and Molecular Medicine. .

Author Information

  1. Yokohama City University, Yokohama, Japan

Publication History

  1. Published Online: 15 SEP 2006

Abstract

Hemoglobin is the oxygen-carrying protein of the blood, binding oxygen at iron-containing heme groups within the protein. Its structure is well characterized in both the deoxy and oxy forms, and comparison of these structures has shown how the protein changes its conformation as the number of bound oxygen molecules increases. These conformations have different ligand affinities, and so the protein can regulate how tightly oxygen is bound. A detailed understanding of the protein mechanism and control of ligand affinity requires the study of mutant proteins. Many mutated hemoglobins have been detected clinically, but these naturally occurring mutants have generally been of limited use in analyzing hemoglobin function. A number of expression systems have therefore been devised to produce human hemoglobin from microorganisms. These systems make possible the alteration of specific residues or groups of residues so that their functional role may be tested. Together with the wide variety of biophysical techniques employed in the study of hemoglobin, genetic engineering has proved to be a powerful tool for testing the function of different parts of the protein. Hemoglobin remains one of the most important systems for testing ideas concerning protein folding and function, protein interactions, and cooperativity. It is far from being completely understood, despite the widespread impression that this is so. The last decade has seen an explosion in hemoglobin research triggered by the ability to create artificial mutants of hemoglobin, and the increasing need for a safe, cheap blood substitute. This review attempts to highlight some of the advances made in recent years.

Keywords:

  • Heme;
  • Distal;
  • Proximal;
  • Allostery;
  • Cooperativity;
  • p50