Liddington, R. et al. 1992. High resolution crystal structures and comparisons of T state deoxyhemoglobin and two liganded T-state hemoglobins. J. Mol. Biol. 228: 551.
Perutz, M. F. 1970. Stereoschemistry of cooperative effects in haemoglobin. Nature. 228: 726-734.
Shaanan, B. 1982. The iron-oxygen bond in human oxyhaemoglobin. Nature. 296: 683.
Shaanan, B. 1983. Structure of human oxyhaemoglobin at 2.1 resolution. J. Mol. Biol. 171: 31.
Each polypeptide chain is made up of eight or nine alpha-helical segments <>and an equal number of nonhelical ones placed at the corners between them and at the ends of the chain. The helices are named A-H, starting from the amino acid terminus, and the nonhelical segments that lie between the helices are named AB, BC, CD, etc. The nonhelical segments at the ends of the chain are called NA at the amino terminus and HC at the carboxyl terminus.
To form the tetramer <>, each of the subunits is joined to its partner around a twofold symmetry axis, so that a rotation of 180 degrees brings one subunit into congruence with its partner. One pair of chains is then inverted and placed on top of the other pair so that the four chains lie at the corners of a tetrahedron. The four subunits are held together mainly by nonpolar interactions and hydrogen bonds. There are no covalent bonds between subunits. The twofold symmetry axis that relates the pairs of alpha and beta chains runs through a water-filled cavity>at the center of the molecule. This cavity widens upon transition form the R structure to the T structure to form a receptor site for the allosteric effector DPG (2,3 diphosphoglycerate) between the two beta chains. The heme group is wedged into a pocket of the globin with its hydrocarbon side chains interior and its polar propionate side chains exterior.
are nine positions in the amino acid sequence that contain the same amino acid
in all or nearly all species studied thus far. These conserved positions are
especially important for the function of the hemoglobin molecule. Several of
them, such as histidines F8 (His87)<> and E7 (His63)<>, are directly involved in the oxygen-binding
site<> . Phenylalanine CD1 (Phe43) <> and leucine F4 (Leu83) <> are also in direct contact with the heme group<>. Tyrosine HC2 (Tyr140) <>stabilizes the molecule by forming a hydrogen bond between the H<> and F helices<>. Glycine B6 (Gly25)<>is conserved because of its small size: a side chain larger than a
hydrogen atom would not allow theB<> and E helices<> to approach each other as closely as they do. Proline
C2 (Pro37)<> is important because it terminates the C
helix. Threonine C4 (Thr39) and lysine H10 (Lys127) are also conserved residues,
but their roles are uncertain.
from the T structure<> to the R structure<> is triggered by stereochemical changes at the hemes. In deoxyhemoglobin,
the iron atom is about 0.6 angstroms out of the heme plane because of steric
repulsion between the proximal histidine and the nitrogen atoms of the porphyrin.
The heme group and proximal histidine make intimate contact with some fifteen
side chains and so the structures of the F helix, the EF corner, and the FG
corner change on oxygenation. These changes are then transmitted to the subunit
interfaces. The expulsion of the tyrosine HC2 from the pocket between the F
and H helices leads to the rupture of interchain salt bridges. Consequently,
the equilibrium between the two quaternary structures is shifted to the R form