title: Esterification of the propionate groups promotes alpha/beta hemoglobin chain homogeneity of CN-hemin binding.
abstract: This study examines the post-translational role of peripheral propionate groups in the incorporation of the Fe-protoporphryin IX heme into nascent alpha- and beta-globin chains. Human apohemoglobin (a heme-free alpha/beta dimer) in 0.05 M potassium phosphate buffer, pH 7, at 20 degrees C was titrated with either CN-protohemin (native heme with two peripheral propionate groups), or CN-dimethylester hemin (a modified heme with two methyl ester groups in place of the propionate groups). Soret spectrophotometric CN-hemin titrations confirmed that a spectral shift resulted upon binding of protohemin, but no spectral shift occurred upon binding the dimethylester derivative. Recent studies have correlated a Soret spectral shift with the preferential heme binding to the alpha subunit of apohemoglobin. The absence of a Soret wavelength shift (in conjunction with molecular modeling) presented here suggested that the modification of heme propionate groups prevented the formation of an alpha-heme/beta-globin intermediate, a requisite step in the normal assembly of functional hemoglobin.
authors.affiliation: Department of Chemistry, University of Massachusetts Lowell, Lowell, MA 01854, USA.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Jennings
authors.forename: Melisenda J
authors.initials: MJ
authors.lastname: McDonald
mesh_terms: D001059:Apoproteins / Q000737:chemistry; D003486:Cyanides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000737:chemistry; D006427:Hemin / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry; D013053:Spectrophotometry
chemical_list: D001059:Apoproteins; D003486:Cyanides; D006454:Hemoglobins; D010446:Peptide Fragments; D011422:Propionates; C023478:apohemoglobin; C070077:alpha(A) globin; D006418:Heme; D006427:Hemin; D007501:Iron