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β141 Leu is not deleted in the unstable haemoglobin Atlanta‐Coventry but is replaced by a novel amino acid of mass 129 daltons
Author(s) -
Brennan Stephen O.,
Shaw John,
Allen John,
George Peter M.
Publication year - 1992
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1992.tb08179.x
Subject(s) - amino acid , chemistry , globin , leucine , biochemistry , peptide , chymotrypsin , molecular mass , cleavage (geology) , gene , stereochemistry , microbiology and biotechnology , biology , trypsin , enzyme , paleontology , fracture (geology)
Reinvestigation of the structure of the β‐chain of Hb Atlanta‐Coventry (β75 Leu→Pro, β141 Leu deleted) confirmed the presence of two abnormalities; however, analysis of the aberrant β Co 14 tryptic peptide by liquid secondary ion mass spectrometry indicated that the β141 Leu (mass 113 daltons) was not deleted but replaced by a novel amino acid of mass 129 daltons. The new amino acid in peptide β Co 14 was uncharged at pH 6·5, more hydrophillic than leucine and susceptible to cleavage by both chymotrypsin and carboxypeptidase A. We propose that the new residue is likely to be hydroxyleucine and that it results from post‐translational oxidation of β141 Leu as a consequence of perturbation of the haem environment caused by the β75 Leu→Pro mutation in the E helix (E19). This proposal is entirely consistent with recent DNA analysis which showed that β At‐Co was not the product of a third β‐globin gene and that neither of the two β‐globin genes. β A nor β Atlanta , contained a deletion of the β141 Leu codon. We have subsequently found this modified amino acid at position β141 in two other unstable haemoglobins, both of which involve mutations on the haem side of the E helix.