Studies on the primary structure of bovine high-molecular-weight kininogen. Amino acid sequence of a fragment ("histidine-rich peptide") released by plasma kallikrein.

An unknown peptide fragment, which was released from bovine high-molecular-weight kininogen by bovine plasma kallikrein [EC 3.4.21.8], was isolated and its chemical structure was established. The fragment consisted of 41 amino acids with serine and arginine at the NH2- and COOH-termini, respectively. The molecular weight was calculated to be 4,584. It was very basic and contained eleven residues each of histidine and glycine and seven residues of lysine. Thus, the total number of these three amino acids accounted for about 70 percent of the total residues constituting the fragment. The amino acid sequence of the fragment, designated tentatively as "His-rich peptide," was studied by Edman degradation and standard enzymatic and chemical techniques. These data made it possible to deduce the following sequence: H-Ser-His-Gly-Leu-Gly-His-Gly-His-Gln-Lys-Gln-His-Gly-Leu-Gly-His-Gly-His-Lys-His-Gly-His-Gly-His-Gly-Lys-His-Lys-Asn-Lys-Gly-Lys-Asn-Asn-Gly-Lys-His-Tyr-Asp-Trp-Arg-OH. The fragment had an extremely interesting feature in that repeating sequences occur along the peptide chain. The repeats were of the type His-Gly-X or Gly-His-X and this sequence appeared six or seven times up to 26 residues from the N-terminal end. Moreover, three tetrapeptide sequences of Gly-His-Gly-His and two heptapeptide sequence consisting of His-Gly-Leu-Gly-His-Gly-His were found in the N-terminal portion. It should be noted that plasma kallikrein liberates such a histidine-rich peptide from the kininogen in addition to a physiologically active peptide, bradykinin. The location of the "His-rich peptide" fragment in the percursor protein is also discussed.