Thermodynamics ribonuclease conformational

Many other examples of outwardly complex molecular structures, whose salient architectural features appear to self-assemble from their constituent building blocks, have been documented [16]. The formation of the DNA double helix from its constituent chains is perhaps the quintessential example, whilst the perfect reconstitution of the intact tobacco mosaic virus from its constituent RNA and protein monomers also exhibits all the hallmarks of a cooperative self-assembly process [17]. The same is true of ribonuclease. Reconstitution of this enzyme in the presence of mercaptoethanol, to allow reversible exchange of the four disulfide bridges, proceeds smoothly to generate eventually only the active conformation from many possible isomeric states [18], In each of these cases, the thermodynamic stability of the product is vital in directing its synthesis. These syntheses could therefore be termed product-directed. 

Among all possible configurations, the active enzyme conformation is assumed to be thermodynamically the most stable in situ. Experimental evidence to validate this assumption came from reversible denaturation studies on enzymes. For example. ribonuclease may be completely unfolded in urea solution after breakage of four native intramolecular disulphide bridges. Afterwards, when ribonuclease is brought to renature in the proper conditions, the native disulphide bonds are restored, and the protein recovers its catalytic activity. This case must be regarded, however, as a very favourable one because in most instances renaturation is... 

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