Complete amino acid sequence of human hemopexin, the heme-binding protein of serum.

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Abstract
The complete primary structure of human hemopexin, a plasma .beta.-glycoprotein that specifically binds 1 heme with high affinity and transports it to hepatocytes for salvage of the iron was determined. Human hemopexin (MW .apprxeq. 63,000) consists of a single polypeptide chain containing 439 amino acid residues with 6 intrachain disulfide bridges. The amino-terminal threonine residue is blocked by an O-linked galactosamine oligosaccharide and the protein has 5 glucosamine oligosaccharides N-linked to the acceptor sequence Asn-X-Ser/Thr. The 18 tryptophan residues are arranged in 4 clusters, and 12 of the trytophans are conserved in homologous positions. Computer-assisted analysis of the internal homology in amino acid sequence indicates that hemopexin consists of 2 similar halves, thus suggesting duplication of an ancestral gene. Limited tryptic digestion cleaves apohemopexin after arginine-216 into 2 half-molecules, whereas heme-saturated hemopexin is cleaved after lysine-101. The half-molecules are connected by a histidine-rich hinge-like region that contains 2 glucosamine oligosaccharides. A structural model for human hemopexin is proposed that is based on these properties and on computer-assisted predictions of the secondary structure and the hydrophilic/hydrophobic character. .alpha.-Helices and .beta.-turns predominate and the 2 halves are connected by an exposed connecting region in apohemopexin that becomes inaccessible to trypsin in heme-saturated hemopexin. Many segments of hemopexin are similar to sequences of other heme proteins, but no overall structural relationship of hemopexin to any other heme protein was identified.