Truncated hemoglobins: trimming the classical 'three-over-three' globin fold to a minimal size

Truncated hemoglobins (trHbs) host the heme in a 'two-over-two' alpha -helical sandwich which results from extensive editing of the classical 'three-over-three' globin fold. The three-dimensional structure of trHbs is based on four main alpha -helices, arranged in a sort of a-helical bundle composed of two antiparallel helix pairs (B/E and G/H). Most notably, trHbs deviate from the conventional globin fold in that they display an extended loop substituting for the heme, proximal F-helix observed in globins. Moreover, since efficient adaptation of a 110-130 amino acid trHb chain to host the porphyrin ring firstly requires specific chain flexibility, trHbs contain three invariant Gly-based motifs. Inspection of the trHb three-dimensional trHb structures shows that an apparent protein cavity or tunnel would connect the protein surface to an inner region very close to the heme distal site. Such a structural feature, never observed before in (non) vertebrate globins, may have substantial implications for ligand diffusion and binding properties in trHbs. (C) 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved.