ARGININE SUBSTITUTIONS IN THE HINGE REGION OF ANTICHYMOTRYPSIN AFFECTSERPIN BETA-SHEET REARRANGEMENT

A hallmark of serpin function is the massive beta-sheet rearrangement involving the insertion of the cleaved reactive loop into beta-sheet A as strand s4A. This structural transition is required for inhibitory activity. Small hydrophobic residues at P14 and P12 positions of the r eactive loop facilitate this transition, since these residues must pac k in the hydrophobic core of the cleaved serpin. Despite the radical s ubstitution of arginine at the P12 position, the crystal structure of cleaved A347R antichymotrypsin reveals full strand s4A insertion with normal beta-sheet A geometry; the R347 side chain is buried in the hyd rophobic protein core. In contrast, the structure of cleaved P14 T345R antichymotrypsin reveals substantial yet incomplete strand s4A insert ion, without burial of the R345 side chain.