Tightening and Untying the Knot in Human Carbonic Anhydrase III.
The forced mechanical unfolding of the knotted protein Human Carbonic Anhydrase (HCA) III is examined by steered, explicit-water molecular dynamics computer simulations. In agreement with previous indications from experiments and coarse-grained simulations, knot tightening by pulling near-terminal amino acids (4 and 267) leads to a much higher resistance to unfolding than for knot untying, where pulling amino acids 4 and 253 untangles the knot by threading the C-terminal end out of the knotting loop. In particular, the resistance during knot tightening is observed to diverge due to a tightly tied-up enzymatic core of the HCA if it is coordinated by the catalytically important zinc ion. The underlying structural pictures are presented and discussed.
Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin, Hahn-Meitner Platz 1, 14109 Berlin, Germany.|Department of Physics, Humboldt-University Berlin, Newtonstr. 15, 12489 Berlin, Germany.
Joachim
J
Dzubiella
entanglement; explicit-water simulations; mechanical unfolding; protein stability; zinc coordination