THE PROBABLE CONFORMATION OF SUBSTRATES RECOGNIZED BY DIPEPTIDYLPEPTIDASE-IV AND SOME ASPECTS OF THE CATALYTIC MECHANISM DERIVED FROM THEORETICAL INVESTIGATIONS

By theoretical conformational investigations of substrates and nonsubstrates of the enzyme dipeptidyl-peptidase IV (DP IV) as well as dipeptide-esters using the ECEPP83 method we determined the structure of peptides recognized and cleaved by the enzyme. From a comparison of all possible structures for the substrates with conformations not possible in nonsubstrates we concluded that a single conformation explains substrate specificities of DP IV. This conformation is characterized by the following dihedral angles: PSI-1 = 85-degrees, omega-1 = 180-degrees, PHI-2 = -75-degrees, PSI-2 = 80-degrees, and omega-2 = 180-degrees. The conclusions were supported by comparisons of molecular electrostatic potentials calculated with the molecular graphics program HAMOG.