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Periodate modification of human serum transferrin Fe(III)-binding sites. Inhibition of carbonate insertion into Fe(III)- and Cu(II)-chelator-transferrin ternary complexes.
Ross, D C; Egan, T J; Purves, L R.
Afiliación
  • Ross DC; Department of Chemical Pathology, University of Cape Town, Red Cross War Memorial Children's Hospital, Rondebosch, South Africa.
J Biol Chem ; 270(21): 12404-10, 1995 May 26.
Article en En | MEDLINE | ID: mdl-7759481
Periodate modification of human serum transferrin produces a species that binds Fe(III) weakly at pH 7.4 contrary to previous reports that Fe(III)-binding activity is completely lost. Ternary complexes of periodate-modified transferrin and either Fe(III) with nitrilotriacetate (NTA), oxalate, citrate, or EDTA, or of Cu(II) with oxalate could be formed. Peak wavelength maxima of these spectral bands are identical to those reported for native transferrin in the absence of bicarbonate. No carbonate ternary complexes of periodate-modified transferrin with Fe(III), Al(III), Cu(II), or Zn(II) could be formed. Conditional (Fe(NTA)) binding constants (log K) for C- and N-terminal modified sites are 7.33 and 7.54, respectively. The respective extinction coefficients at 470 nm are decreased 45% compared with the native protein. The electron paramagnetic resonance spectrum of the complex closely resembles that of the Fe(III)-NTA ternary complex formed with native transferrin in the absence of bicarbonate. Anions, including bicarbonate, at high concentrations destabilize formation of this Fe(III)-NTA ternary complex, while Fe(III) chelators readily remove the bound Fe(III). Bicarbonate, sulfate, and pyrophosphate still bind to the modified binding sites in the absence of metal although with slightly lower affinity and with lower molar difference absorptivities. Results are interpreted as an inhibition of a crucial protein conformational change by an intramolecular cross-link, preventing formation of the particularly stable metal-carbonate ternary complex from the less stable metal-chelate ternary complex. The method can be used to produce monosited transferrins.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoproteínas / Transferrina / Compuestos Férricos / Hierro Límite: Humans Idioma: En Revista: J Biol Chem Año: 1995 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoproteínas / Transferrina / Compuestos Férricos / Hierro Límite: Humans Idioma: En Revista: J Biol Chem Año: 1995 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Estados Unidos