A Ubiquitously Expressed Human Hexacoordinate Hemoglobin

Abstract

We have identified a new human hemoglobin that we call histoglobin because it is expressed in a wide array of tissues. Histoglobin shares less than 30% identity with the other human hemoglobins, and the gene contains an intron in an unprecedented location. Spectroscopic and kinetic experiments with recombinant human histoglobin indicate that it is a hexacoordinate hemoglobin with significantly different ligand binding characteristics than the other human hexacoordinate hemoglobin, neuroglobin. In contrast to the very high oxygen affinities displayed by most hexacoordinate hemoglobins, the biophysical characteristics of histoglobin indicate that it could facilitate oxygen transport. The discovery of histoglobin demonstrates that humans, like plants, differentially express multiple hexacoordinate hemoglobins.

Cytoglobin, a Novel Member of the Globin Family, Protects Kidney Fibroblasts against Oxidative Stress under Ischemic Conditions

“…Cygb shows the same order of oxygen affinity as does myoglobin, which suggests that it may facilitate oxygen diffusion into the mitochondrial respiratory chain. 4 On this basis, up-regulation of Cygb in the hypoxic kidney may be an adaptive response to increase the efficiency of mitochondrial respiration under oxygen deprivation states. In addition, oxidative stress likely mediates many of the deleterious effects of I/R injury, 36,37 with the tubulointerstitium as the main target.…”

“…This protein was subsequently identified in the expressed sequence tag databases from zebrafish, mouse, and human, and was renamed Cygb. 4,5 Serial studies clarified that Cygb was localized in splanchnic fibroblasts of various organs. 3,6 In the normal rat, findings at immunohistochemical analysis suggested that Cygb-positive cells are positive for HSP47, a collagen-specific molecular chaperone of the kidney and intestine, and also for CD73, a marker of renal cortical fibroblast-like cells, in the normal rat kidney interstitium.…”

Slow Ligand Binding Kinetics Dominate Ferrous Hexacoordinate Hemoglobin Reactivities and Reveal Differences between Plants and Other Species

“…Ferrous bis-histidyl heme has a characteristic absorption spectrum exemplified by cytochrome b 5 . Plant hxHbs were the first hemoglobins to be identified with a similar spectrum (19,22).…”

“…Oxygen transport in many animals and in the root nodules of nitrogen fixing plants is facilitated by "pentacoordinate" hemoglobins with open heme-iron sites that favor unhindered reversible oxygen binding (4). Plants, animals, and some cyanobacteria also contain Hbs that differ from traditional oxygen transport proteins because of a common structural feature: a histidine side chain reversibly binds to the sixth coordination site of the heme iron in both the ferric and ferrous forms of each protein (5)(6)(7). For this reason, these proteins have been termed "hexacoordinate" Hbs (hxHbs).…”

Cloning, expression and purification of Atlantic salmon (Salmo salar, L.) neuroglobin

“…Neuroglobin (Ngb) is a recently discovered globin [1][2][3][4] and it is thought to be of ancient evolutionary origin. Ngb is found in all vertebrates in small amounts, and is expressed mainly in nervous tissues [1].…”