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Multiple Stable Conformations Account for Reversible Concentration‐Dependent Oligomerization and Autoinhibition of a Metamorphic Metallopeptidase
Author(s) -
LópezPelegrín Mar,
CerdàCosta Núria,
CintasPedrola Anna,
HerranzTrillo Fátima,
Bernadó Pau,
Peinado Juan R.,
Arolas Joan L.,
GomisRüth F. Xavier
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201405727
Subject(s) - chemistry , energy landscape , conformational isomerism , biophysics , enzyme , structural plasticity , stereochemistry , biochemistry , biology , molecule , organic chemistry , neuroscience
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.