TY - JOUR
T1 - Properties of human hemoglobins with increased polarity in the α- or β-heme pocket
T2 - Carbonmonoxy derivatives
AU - Karavitis, Michael
AU - Fronticelli, Clara
AU - Brinigar, William S.
AU - Vasquez, Gregory B.
AU - Militello, Valeria
AU - Leone, Maurizio
AU - Cupane, Antonio
PY - 1998/9/11
Y1 - 1998/9/11
N2 - The spectroscopic, conformational, and functional properties of mutant carbonmonoxy hemoglobins in which either the β-globin Val67(E11) or the α-globin Val62(E11) is replaced by threonine have been investigated. The thermal evolution of the Sorer absorption band and the stretching frequency of the bound CO were used to probe the stereodynamic properties of the heme pocket. The functional properties were investigated by kinetic measurements. The spectroscopic and functional data were related to the conformational properties through molecular analysis. The effects of this nonpolar-to-polar isosteric mutation are: (i) increase of heme pocket anharmonic motions, (ii) stabilization of the A(o) conformer in the IR spectrum, (iii) increased CO dissociation rates. The spectroscopic data indicate that for the carbonmonoxy derivatives, the Val → Thr mutation has a larger conformational effect on the β-subunits than on the α-subunits. This is at variance with the deoxy derivatives where the conformational modification was larger in the heme pocket of the α-subunit (Cupane, A., Leone, M., Militello, V., Friedman, R. K., Koley, A. P., Vasquez, G. P., Brinigar, W. S., Karavitis, M., and Fronticelli, C. (1997) J. Biol. Chem. 272, 26271-26278). These effects are attributed to a different electrostatic interaction between O(γ) of Thr(E11) and the bound CO molecule. Molecular analysis indicates a more favorable interaction of the bound CO with Thr O(γ) in the β-subunit heme pocket.
AB - The spectroscopic, conformational, and functional properties of mutant carbonmonoxy hemoglobins in which either the β-globin Val67(E11) or the α-globin Val62(E11) is replaced by threonine have been investigated. The thermal evolution of the Sorer absorption band and the stretching frequency of the bound CO were used to probe the stereodynamic properties of the heme pocket. The functional properties were investigated by kinetic measurements. The spectroscopic and functional data were related to the conformational properties through molecular analysis. The effects of this nonpolar-to-polar isosteric mutation are: (i) increase of heme pocket anharmonic motions, (ii) stabilization of the A(o) conformer in the IR spectrum, (iii) increased CO dissociation rates. The spectroscopic data indicate that for the carbonmonoxy derivatives, the Val → Thr mutation has a larger conformational effect on the β-subunits than on the α-subunits. This is at variance with the deoxy derivatives where the conformational modification was larger in the heme pocket of the α-subunit (Cupane, A., Leone, M., Militello, V., Friedman, R. K., Koley, A. P., Vasquez, G. P., Brinigar, W. S., Karavitis, M., and Fronticelli, C. (1997) J. Biol. Chem. 272, 26271-26278). These effects are attributed to a different electrostatic interaction between O(γ) of Thr(E11) and the bound CO molecule. Molecular analysis indicates a more favorable interaction of the bound CO with Thr O(γ) in the β-subunit heme pocket.
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U2 - 10.1074/jbc.273.37.23740
DO - 10.1074/jbc.273.37.23740
M3 - Article
C2 - 9726982
AN - SCOPUS:0032508540
SN - 0021-9258
VL - 273
SP - 23740
EP - 23749
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -