Application of linear free energy relations to protein conformational changes: the quaternary structural change of hemoglobin.

Abstract

The transition state for the R = T quaternary conformational change of hemoglobin has thermodynamic properties much closer to those of the R conformation than to those of the T conformation. This finding is based on a comparison of activation and equilibrium enthalpy and entropy changes and on the observation of a linear free energy relationship between quaternary rate and equilibrium constants. A previous theoretical study [Janin, J. & Wodak, S. J. (1985) Biopolymers 24, 509-526], using a highly simplified energy function, suggests that the R-like transition state is the result of a reaction pathway with the maximum buried surface area

Funnels, pathways, and the energy landscape of protein folding: A synthesis

“…In the past these relations have been applied to the interpretation of data from site-directed mutagenesis experiments [111][112][113][114]. They are also the mainstay of the analysis of many other biochemical reactions [115][116][117]. In this analysis the differences in the free energies of the transition states, folded states and unfolded states for two different sequences are obey the linear relation…”

Multiple strategies for O2 transport: from simplicity to complexity

“…The efficiency of the pump is primarily due to the strong pH dependence of the functional heterogeneity of trout HbIV (Fig. 4), which is considerably greater at the higher saturations associated with high O 2 pressure (116).…”

“…The downhill flow of H þ , which is maintained at high concentration in the swim bladder, provides the free energy necessary to pay for the opposite, uphill, flow of O 2 ; the overall thermodynamic process being of course symmetric with respect to the two ligands (116).…”

“…The maintenance of the pH gradient, which ensures continuing operation of the system, is due to the metabolism of the fish. It is known that the gas gland, associated to the swim bladder, produces large amounts of lactic acid even in the presence of O 2 (116,121).…”

“…Thus, at moderately acid pH values (i.e., 56.5), trout HbIV is incompletely saturated even at atmospheric O 2 pressure, a phenomenon called 'Root effect' (93,108). Detailed investigation on the pH dependence for O 2 and CO binding (116,117) clearly envisaged a more complex behavior than for trout HbI. Thus, a marked pH dependence of the ligand binding isotherms is accompanied by a dramatic pH dependence of cooperativity, which underlies a linkage between H þ and the allosteric equilibrium (Fig.…”