Document Type
Article
Publication Title
Journal of Biological Chemistry
Publication Date
1989
Volume
264
Issue
19
Disciplines
Medical Sciences | Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
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-A resolution indicate that a covalent adduct is formed between the ligand and residues Lys-82 EF6 of each beta 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 degrees C). The subunit cooper-activity of di-ATP Hb is also reduced (nmax = 1.9 versus 2.7 control).
Rights
© 1989 The American Society for Biochemistry and Molecular Biology, Inc.
Recommended Citation
Kavanaugh, Michael; Perutz, Max F.; Fermi, Giulio; Shih, Daniel T.; and Jones, Richard T., "Structure and function of human hemoglobin covalently labeled with periodate-oxidized adenosine triphosphate" (1989). Biomedical and Pharmaceutical Sciences Faculty Publications. 60.
https://scholarworks.umt.edu/biopharm_pubs/60
