Structure and Reactivity of Hexacoordinate Hemoglobins

Abstract

The term "hemoglobin" has spent decades at the forefront of biochemical research, including the eras of "grind-and-find", protein structure determination, and the relationship between protein structure and function. It has also served as a familiar target in genomic annotation, and as a guidepost to study the evolution of primary structure and protein function. We have learned over the past fifteen years that most organisms contain genes with homology to globins, and that not all glo- AbstractThe heme prosthetic group in hemoglobins is most often attached to the globin through coordination of either one or two histidine side chains. Those proteins with one histidine coordinating the heme iron are called "pentacoordinate" hemoglobins, a group represented by red blood cell hemoglobin and most other oxygen transporters. Those with two histidines are called "hexacoordinate hemoglobins", which have broad representation among eukaryotes. Coordination of the second histidine in hexacoordinate Hbs is reversible, allowing for binding of exogenous ligands like oxygen, carbon monoxide, and nitric oxide. Research over the past several years has produced a fairly detailed picture of the structure and biochemistry of hexacoordinate hemoglobins from several species including neuroglobin and cytoglobin in animals, and the nonsymbiotic hemoglobins in plants. However, a clear understanding of the physiological functions of these proteins remains an elusive goal.