Conformation in solution of hemoglobin Osler (alpha 2 A beta 2 145 Tyr replaced by Asp).

Abstract

Computer simulations of Gelin and Karplus ((1977) Proc. Natl. Acad. Sci. U.S.A. 74, 801-805) suggest that in hemoglobin upon ligation the penultimate tyrosyl residues of the subunits are not expelled from the hydrophobic pockets described in the crystals between the helices E and F (Perutz, M.F. (1970) Nature 228, 726-737). This implies that both the liganded and unliganded conformations of hemoglobin may be affected by mutations involving such residues. Investigation of the conformational behavior of liganded and unliganded hemoglobin Osler was conducted measuring the functional properties, the subunits dissociation, the CD and electronic spectra, the protons absorption upon interaction with polyanions, and the reactivity of the -SH groups of the protein. The results suggest that both the liganded and unliganded conformations of the system are affected by the mutation, confirming the anticipations of Gelin and Karplus on the relevance of tyrosine at beta 145 for both allosteric states of hemoglobin.