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Publication Abstract from PubMed

Molecular plasticity controls enzymatic activity: the native fold of a protein in a given environment is normally unique and at a global free-energy minimum. Some proteins, however, spontaneously undergo substantial fold switching to reversibly transit between defined conformers, the "metamorphic" proteins. Here, we present a minimal metamorphic, selective, and specific caseinolytic metallopeptidase, selecase, which reversibly transits between several different states of defined three-dimensional structure, which are associated with loss of enzymatic activity due to autoinhibition. The latter is triggered by sequestering the competent conformation in incompetent but structured dimers, tetramers, and octamers. This system, which is compatible with a discrete multifunnel energy landscape, affords a switch that provides a reversible mechanism of control of catalytic activity unique in nature.

Multiple stable conformations account for reversible concentration-dependent oligomerization and autoinhibition of a metamorphic metallopeptidase.,Lopez-Pelegrin M, Cerda-Costa N, Cintas-Pedrola A, Herranz-Trillo F, Bernado P, Peinado JR, Arolas JL, Gomis-Ruth FX Angew Chem Int Ed Engl. 2014 Sep 26;53(40):10624-30. doi: 10.1002/anie.201405727., Epub 2014 Aug 27. PMID:25159620^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.