Predicted effect of the Gly11Asp mutation on the conformation of the protein S Gla domain.

The Gla domain of protein S shown was derived by homology modeling and refinement.36 In order to predict the effects of the Gly11Asp amino acid substitution on protein S structure and function, the Insight II 3D Graphics Program (Accelrys, San Diego, CA) was used. The alpha-carbon backbone trace is shown in dark gray ribbon representation. The side-chain of Asp11 (mutated from Gly11) is depicted in thick stick representation shaded by atom type. The side-chain of Gla29 is depicted in ball-and-stick style, also colored by atom (carbon, pale gray; oxygen, mid-gray). Two Ca²⁺ions that are coordinated (black lines) by the Gla29 side-chain are shown as very pale spheres. Replacement of wild-type Gly11 by Asp causes multiple bad contacts with atoms of the neighboring Gla29 side-chain, likely to result in loss of Ca²⁺ ion coordination, Ca²⁺ ion affinity, and destabilization of the Ca²⁺-dependent conformation of the Gla domain that is required for interaction with phospholipids.