Partially Folded Protein Is Catalytically Active

Researchers have discovered that a partially folded enzyme is catalytically active, even though its active site is not in its native-state shape. In fact, the site adopts a variety of conformations. The findings help confirm that biological function need not be dependent on unique three-dimensional shapes. By making absorbance measurements of an optically absorbing substrate, Fabrizio Chiti of the University of Florence, in Italy, and coworkers were able to observe increases in enzymatic activity while a microbial acylphosphatase was still folding—even though the structure of its active site was changing (EMBO J., DOI: 10.1038/emboj.2008.82). The activity was appreciable—about 80% of that exhibited by the fully folded protein. Other groups have found that partially unfolded and intrinsically disordered proteins can play active roles in biological processes. The new study extends this idea by helping to confirm that "a conformational state structurally distant from the folded structure ... is able to bind substrates, carry out catalysis, and release products," Chiti and coworkers note.