A STRUCTURAL MODEL FOR THE GLUTAMATE-SPECIFIC ENDOPEPTIDASE FROM STREPTOMYCES-GRISEUS THAT EXPLAINS SUBSTRATE-SPECIFICITY

We present a model for the three-dimensional structure of the glutamat e-specific endopeptidase from Streptomyces griseus based on the crysta l structures of other bacterial proteases of the trypsin family. For t he first time a structural model is described which attempts to explai n the basis of P1 glutamate specificity in serine proteases. Several i mportant changes to the S1 pocket with respect to other members of the family of different specificity are described. Of particular interest is the presence of a histidine at position 213 and the substitution o f Arg-138 by lysine. Other biochemical evidence concerning substrate p references can be rationalized on the basis of the model.