One Size Fits Many

+ See all authors and affiliations

Science  17 Sep 2004:
Vol. 305, Issue 5691, pp. 1679-1681
DOI: 10.1126/science.305.5691.1679d

Enzymatic reactions generally demand a precise positioning of catalytic residues; thus, structural disorder in a protein might be expected to be inconsistent with catalytic prowess. However, Vamcava et al. show that a monomeric chorismate mutase (mCM), obtained by redesign of the naturally occurring dimer, displays many of the characteristics of a molten globule yet still possesses one-third of the wild-type catalytic efficiency. Spectroscopic and thermal denaturation experiments all suggest that the monomeric form has high conformational flexibility and only adopts an ordered structure when a transition-state analog (inhibitor) is added. In contrast, dimeric CM is ordered both in the absence and presence of ligand. The polar character of the active site in the interior of mCM, unlike the hydrophobic core of the wild-type enzyme, fails to rigidify the folded state. When the inhibitor binds, it fills the pocket and supplies interactions that propagate and improve global ordering, as in the induced fit model of enzyme catalysis, in which the catalytically active conformation is locked into place as the reaction progresses. The idea that folding and catalysis can be linked implies that modern-day enzymes could have evolved from molten globules. Perhaps, a primordial structural plasticity conferred relaxed substrate specificity enabling a limited set of protein enzymes to catalyze a wide range of reactions. — VV

Proc. Natl. Acad. Sci. U.S.A. 101, 12860 (2004).

Related Content

Navigate This Article