Biochemistry

Close Enough

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Science  30 May 2008:
Vol. 320, Issue 5880, pp. 1135
DOI: 10.1126/science.320.5880.1135a

The classical view that protein function is associated with a well-defined three dimensional fold has been eroded, slightly, by the discoveries that intrinsically disordered proteins do exist and that disorder might play an important role in protein interactions. Catalysis would seem more structurally demanding. Although it is increasingly recognized that dynamics contributes to enzyme activity, most would have assumed that this occurs in the context of a folded protein; nevertheless, catalytic activity has been observed in an engineered enzyme with molten globule properties, where activity is apparently coupled to substrate-induced folding. Bemporad et al. show that the partially folded Sulfolobus solfataricus acylphosphatase is active and that this does not derive from a global substrate-induced folding. Molecular dynamics simulations revealed that an ensemble of partly folded molecules is characterized by substantial structural flexibility of the catalytic region; the remainder of the protein forms a scaffold that restricts the conformational space of the flexible region so that in a large fraction of the ensemble, residues important for catalysis remain close together. The authors suggest that scaffold regions in proteins might allow functional regions to mutate without compromising overall stability, thus facilitating the evolution of new activities. It remains to be seen if this is a rare case or whether catalysis in the absence of well-defined folded structure is a more common but underappreciated enzyme property. — VV

EMBO J. 27, 10.1038/emboj.2008.82 (2008).

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