4xag

Cycles of destabilization and repair underlie the evolution of new enzyme function

spinqualitylabelsall models 4xag, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4xag is a 2 chain structure with sequence from Brevundimonas diminuta. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CAC, KCX, MPD, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A060GPQ0_BREDI Publication Abstract from PubMed Enzymes must be ordered to allow the stabilization of transition states by their active sites, yet dynamic enough to adopt alternative conformations suited to other steps in their catalytic cycles. The biophysical principles that determine how specific protein dynamics evolve and how remote mutations affect catalytic activity are poorly understood. Here we examine a 'molecular fossil record' that was recently obtained during the laboratory evolution of a phosphotriesterase from Pseudomonas diminuta to an arylesterase. Analysis of the structures and dynamics of nine protein variants along this trajectory, and three rationally designed variants, reveals cycles of structural destabilization and repair, evolutionary pressure to 'freeze out' unproductive motions and sampling of distinct conformations with specific catalytic properties in bi-functional intermediates. This work establishes that changes to the conformational landscapes of proteins are an essential aspect of molecular evolution and that change in function can be achieved through enrichment of preexisting conformational sub-states. The role of protein dynamics in the evolution of new enzyme function.,Campbell E, Kaltenbach M, Correy GJ, Carr PD, Porebski BT, Livingstone EK, Afriat-Jurnou L, Buckle AM, Weik M, Hollfelder F, Tokuriki N, Jackson CJ Nat Chem Biol. 2016 Sep 12. doi: 10.1038/nchembio.2175. PMID:27618189 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotriesterase 3D structures

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