Neighboring bonds, conformational changes

Asp-271 and by the intersubunit link between Glu-239 and both Lys-164 and Tyr-165 Arg-229 is bent out of the active site and interacts with Glu-272. In the R state, the 240s loop shifts to allow interactions between Glu-233 and both Lys-164 and Tyr-165 and between Glu-50 and both Arg-167 and Arg-234 the interaction between Arg-229 and Glu-272 is broken, and a new bond between Arg-229 and Glu-233 stabilizes the R state and helps to position Arg-229 to interact with the j3-carboxylate of aspartate. Accordingly, the interaction of aspartate with Arg-229 breaks the Arg-229-Glu-272 interaction allowing movement of the 240s loop, which is transmitted to the neighboring subunit. This quaternary conformational change leads to loss of contacts that stabilize the T state and formation of new contacts to stabilize the R state. 

Conformational changes in macromolecules must be cooperative processes since, at least for regular conformational sequences, each conformation must be influenced by the conformation of neighboring bonds. An equilibrium constant can be defined for each individual conformational transition. 

Conformational changes in macromolecules must be cooperative processes since, at least for regular conformational sequences, each conformation must be influenced by the conformation of neighboring bonds. An equilibrium constant can be defined for each individual conformational transition. The different conformations can be distinguished from each other by the symbols A and B. A and B can, for example, be trans or gauche conformations or even the cis and trans positions of the peptide groups in poly(proline), etc. 

Glycine residues have more conformational freedom than any other amino acid, as discussed in Chapter 1. A glycine residue at a specific position in a protein has usually only one conformation in a folded structure but can have many different conformations in different unfolded structures of the same protein and thereby contribute to the diversity of unfolded conformations. Proline residues, on the other hand, have less conformational freedom in unfolded structures than any other residue since the proline side chain is fixed by an extra covalent bond to the main chain. Another way to decrease the number of possible unfolded structures of a protein, and hence stabilize the native structure, is, therefore, to mutate glycine residues to any other residue and to increase the number of proline residues. Such mutations can only be made at positions that neither change the conformation of the main chain in the folded structure nor introduce unfavorable, or cause the loss of favorable, contacts with neighboring side chains. 

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