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.