Human serum histidine-rich glycoprotein. I. Interactions with heme, metal ions and organic ligands.
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Morgan WT
Human serum histidine-rich glycoprotein. I. Interactions with heme, metal ions and organic ligands.
Biochim Biophys Acta. 1978 Aug 21;535(2):319-33. doi: 10.1016/0005-2795(78)90098-3.
- PubMed ID
- 678554 [ View in PubMed]
- Abstract
The 3.8 S alpha2-histidine-rich glycoprotein of human serum is composed of two non-identical subunits, each of which contains carbohydrate. The far ultraviolet circular dichroism spectrum of alpha2-histidine glycoprotein indicates that the protein has little alpha-helix but apparently appreciable amounts of beta-sheet and non-regular structures. alpha2-Histidine-rich glycoprotein binds heme with concomitant changes in the electrophoretic mobility of the protein, in the fluorescence of tryptophan residues, and in the absorption and optical activity of the heme chromophore. By fluorescence quenching, the stoichiometry of binding is 1 heme per alpha2-histidine-rich glycoprotein molecule with an apparent Kd near 1.5 muM; however, by changes in absorbance, the interaction of 9 to 10 additional heme molecules with the alpha protein can be detected. The absorption spectra of heme . alpha2-histidine-rich glycoprotein complexes resemble those of low-spin hemoproteins. The ellipticity induced in the heme chromophore on binding by alpha2-histidine-rich glycoprotein increases linearly up to about 10 hemes bound per mol protein. No change in the conformation of alpha2-histidine-rich glycoprotein was indicated by circular dichroism when one or two heme molecules are bound by the protein. alpha2-Histidine-rich glycoprotein does not effectively compete with human serum albumin for heme, suggesting that alpha2-histidine-rich glycoprotein has no major function in serum heme transport. Nonetheless, the binding of heme by alpha2-histidine-rich glycoprotein provides a means of studying the structure of this protein using the heme chromophore as a probe. alpha2-Histidine-rich glycoprotein also binds other organic molecules including bilirubin, diaquocobinamide, Cibacron blue F3GA and rose bengal, and certain divalent metals. It is of interest that copper, zinc, nickel, cadmium and cobalt effectively inhibit the binding of heme by alpha2-histidine-rich glycoprotein, whereas other divalent metals tested, including calcium, magnesium and manganese do not appreciably affect the heme-alpha2-histidine-rich glycoprotein interaction.