Structure and function of human hemoglobin covalently labeled with periodate-oxidized adenosine triphosphate

M. P. Kavanaugh, M. F. Perutz, G. Fermi, D. T. Shih, R. T. Jones

Research output: Contribution to journalArticlepeer-review

Abstract

Periodate-oxidized adenosine triphosphate (o-ATP), a ribose ring-opened dialdehyde derivative of ATP, reacts specifically with human deoxyhemoglobin to give a single major covalently modified product after reduction with sodium borohydride. This product, designated di-ATP Hb, was isolated using ion-exchange chromatography and shown to have incorporated two molecules of o-ATP/tetramer. Peptide mapping and x-ray crystallography at 2.8-Å resolution indicate that a covalent adduct is formed between the ligand and residues Lys-82 EF6 of each β chain in the organic phosphate-binding site of the molecule. di-ATP Hb exhibits a significantly decreased oxygen affinity (P50 = 20.8 mm Hg versus 5.8 mm Hg control; 50 mM 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)-propane-1,3-diol, pH 7.4, 0.1 M C, 20°C). The subunit cooperativity of di-ATP Hb is also reduced (n(max) = 1.9 versus 2.7 control).

Original languageEnglish
Pages (from-to)11009-11013
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number19
StatePublished - 1989

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