Conformational flexibility, biological functioning

SAR studies on melatonin analogues showed that methoxy and amido moieties are important for binding to melatonin receptors various substituents on the 2nd position of the indole ring enhance the binding affinity [52-54]. The conformational flexibility of the C-3 ethylamido side chain is probably responsible for the broad spectrum of biological activities. As a powerful antioxidant melatonin was shown to have significantly broader actions including oncostatic effects [55], immune system stimulation [56], and antiinflammatory functions [57,58]. 

Biomolecular recognition is mediated by water motions, and the dynamics of associated water directly determine local structural fluctuation of interacting partners [4, 9, 91]. The time scales of these interactions reflect their flexibility and adaptability. For water at protein surfaces, the studies of melittin and other proteins [45, 46] show water motions on tens of picoseconds. For trapped water in protein crevices or cavities, the dynamics becomes much slower and could extend to nanoseconds [40, 71, 92], These rigid water molecules are often hydrogen bonded to interior residues and become part of the structural integrity of many enzymes [92]. Here, we study local water motions in various environments, from a buried crevice to an exposed surface using site-selected tryptophan but with different protein conformations, to understand the correlation between hydration dynamics and conformational transitions and then relate them to biological function. 

Like the other macromolecular constituents of the cell (membranes, polynucleotides), the proteins of these extreme thermophiles must also be stable enough to resist heat-induced destruction of conformation and covalent structure. Since virtually all proteins (functional as well as structural proteins) exhibit dynamic properties to fulfill the demands of the living cell, their structure must provide a compromise between rigidity and flexibility, allowing not only stability but also conformational freedom for their biological function at the respective temperature. This means they are not only thermoresistant but require the higher temperature for optimal function. 

Deslauriers, R., McGregor, W. II., Sarantakis, D., and Smith, I. . P. (1974). Biochemistry 13, 3443. Carbon-13 Nuclear Magnetic Resonance Studies of Structure and Function in Thyrotropin-Releasing Factor. Determination of the Tautomeric Form of Histidine and Relationship to Biology Activity. Deslauriers, R., Paiva, A. . M., Schaumburg, K., and Smith, I. . P. (1975). Biochemistry 14, 878. Conformational Flexibility of Angiotensin II. A Carbon-13 Spin-Lattice Relaxation Study. 

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