Conservation and diversity of ancient hemoglobins in Bacteria.

A group of single-domain proteins in Bacteria similar to thermoglobin, an oxygen-avid hemoglobin representative of the ancestral form, reveals the primordial structure, function, and evolvability of the family. Conserved residues at specific positions function to bind ligand or participate in hydrophobic packing of the protein core during protein folding. A potential hydrogen bond network consisting of a tyrosine and glutamine residue in the distal ligand-binding site of most hemoglobins suggests that the ancestral protein bound oxygen avidly. Two divergent hemoglobins with mutations at generally conserved positions contain non-canonical ligand-binding sites, illustrating plasticity of the fold. One binds heme in a manner similar to cytochromes and may represent an evolutionary link to the precursor of the hemoglobin fold. Conservation suggests specific biochemical properties of the ancestral protein; diversity suggests an evolvability of this group of hemoglobins tolerant of mutations that perturb conserved biochemical properties for adaptation to novel functions.