Induced conformational changes

We now examine the extent of conformational changes induced by the binding process. Since for any X we must have 

Instead of examining the nonlinear function X (X) in the range 0 X , it is more convenient to study the function XJQ) in the range 1 0 1. By eliminating 

When h=, i.e., t/ = /, the ligand has no preference for binding on L or on H. Therefore, for any finite value of K the ligand cannot induce conformational change. 

For /i — oo, in which case binding on H is overwhelmingly preferable relative to L, we have = -1/(1 + K) = -X. Therefore, as K becomes very small, i.e., X 1, we have —1, which means that almost all of 

In section 2.10 we made a detailed analysis of the conformational changes induced by the ligand. The system discussed in the present section is essentially the same as the one treated in section 2.10 with the additional feature that there are two sites per polymer instead of one. We shall therefore extend the treatment of section 2.10 to include only this new feature of the present model. 

We start with the differential shift in the equilibrium concentration of, say, the L form, which is defined in Eq. (2.10.69). 

In our model we can ask two questions regarding the equilibrium shift, say of the L form, induced by the binding of either the first or the second ligand. Clearly the first ligand has exactly the same effect as in (3.2.63). The first ligand that binds to the polymer with the initial equilibrium concentration x l clearly does not know of the effect of the second site. In the notation of the present section, the appropriate differential shift is 

The shift caused by the binding of the second ligand is likewise defined by 

for /z 1 this will always be positive, for the same reason as above. Note that (3.2.66) is obtained from (3.2.64) by replacing Khy Kh. This is understandable since the second ligand approaching the polymer sees a singly occupied polymer with equilibrium constant of Kh, which may be obtained simply by putting 0 = 1 in Eq. (2.10.65). Therefore the effect of the second ligand is formally the same as that of the first but with the modified constant Kh instead of K. 

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Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

Leal LG (1986) In Rabin Y (ed) Studies of flow-induced conformation changes in dilute polymer solutions, Proceedings of the 1985 La Jolla Institute Workshop, Academic International Press, New York, p 5... 

The drying protoplast will be subjected to tension as the result of volume contraction and its adherence to the cell wall. Early observations (Steinbrick, 1900) on desiccation tolerant species showed that the protoplasm does not separate from the wall, but rather that it folds and cavities develop in the wall. Where there are thick-walled cells, localised separation of the plasmalemma from the wall may occur. It seems unlikely, however, that rupture of the plasmalemma normally occurs during desiccation. A more subtle form of membrane damage may arise from dehydration-induced conformational changes. Certainly it is relatively easy to demonstrate that dehydrated membranes exhibit a loss of functional integrity... 

Figure 7-5. Two-dimensional representation of Koshland s induced fit model of the active site of a lyase. Binding of the substrate A—B induces conformational changes In the enzyme that aligns catalytic residues which participate in catalysis and strains the bond between A and B, facilitating its cleavage.

Percherancier Y, Berchiche YA, Slight 1, Volkmer-Engert R, Tamamura H, Fujii N, Bouvier M, Heveker N (2005) Bioluminescence resonance energy transfer reveals hgand-induced conformational changes in CXCR4 homo- and heterodimers. J Biol Chem 280 9895-9903... 

Lowering the temperature in the lipase-catalyzed resolution usually enhances the enantioselectivity. The phenomenon does not come from the temperature-induced conformational change of lipase, but it is understandable on the basis of the theory of physical organic chemistry as explained below. ... 

Recent work in our laboratory has shown that Fourier Transform Infrared Reflection Absorption Spectroscopy (FT-IRRAS) can be used routinely to measure vibrational spectra of a monolayer on a low area metal surface. To achieve sensitivity and resolution, a pseudo-double beam, polarization modulation technique was integrated into the FT-IR experiment. We have shown applicability of FT-IRRAS to spectral measurements of surface adsorbates in the presence of a surrounding infrared absorbing gas or liquid as well as measurements in the UHV. We now show progress toward situ measurement of thermal and hydration induced conformational changes of adsorbate structure. The design of the cell and some preliminary measurements will be discussed. 

Gether U, Lin S, Ghanouni P, Ballesteros JA, Weinstein H, Kobilka BK. Agonists induce conformational changes in transmembrane domains III and VI of the beta2 adrenoceptor. EMBO J 1997 16(22) 6737-6747. 

Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK. Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Nad Acad Sci U S A 2001 98(ll) 5997-6002. 

Loo, J. A. Loo, R. R. O. Udseth, H. R. Edmonds, C. G. Smith, R. D. Solvent-induced conformational-changes of polypeptides probed by electrospray-ionization mass-spectrometry. Rapid Comm. Mass Spectrom. 1991,5,101-105. 

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