Structure of human hemopexin: O-glycosyl and N-glycosyl sites and unusual clustering of tryptophan residues.

Abstract

The primary structure of human hemopexin is being deduced from sequence analysis of a series of peptides obtained from chemical and enzymatic digests of the protein. Human hemopexin consists of .apprx. 440 amino acid residues. It has 5 sites of attachment of glucosamine oligosaccharides at the signal sequence of Asn-X-Thr/Ser. A unique structural feature is the virtual blocking of the amino-terminal threonine residue, which is O-linked to a galactosamine oligosaccharide that has not previously been identified in this protein. The galactosamine oligosaccharide and 1 glucosamine oligosaccharide are located in the amino-terminal region, 3 of the glucosamine oligosaccharides are in the middle region, and 1 glucosamine oligosaccharide is in the carboxyl-terminal region of the protein. Two of the 5 glucosamine oligosaccharides are present in a histidine-rich sequence of the middle region of the protein, in which the histidines flank .beta.-turns presuambly at the surface of hemopexin. Clusters of tryptophan residues occur in 4 regions, each of which contains 3 or 4 tryptophan residues separated by 0-12 other residues. This clustering is significant because both histidine and tryptophan have been implicated in the binding of heme. A computer analysis did not identify significant matches of human hemopexin to any protein, including cytochromes and other heme-binding proteins, which suggests that the human hemopexin gene evolved from a unique primordial gene differing from those of other heme-binding proteins.