Electrostatic lock-and-key model for the study of biological isosterism: role of structural water in the binding of basic pancreatic trypsin inhibitor to beta-trypsin.
We propose the electrostatic lock-and-key model for the analysis of the interaction between beta-trypsin and basic pancreatic trypsin inhibitor (BPTI). Prerequisite for the proper recognition of the ligand by the protein is that, beside a steric complementarity, matching of electrostatic patterns is attained. It is found that the complementarity is imperfect in the vicinity of BPTI backbone carbonyl oxygen atoms and this imperfection is diminished by the presence of structural water molecules bound to the contact surface. Some novel types of biological isosteres are proposed. It is expected that the Gibbs free energy of binding increases upon changing the moieties greater than C = O ... H-OH and greater than C = O to greater than CHCH2 CH2OH and greater than CHOH groups, respectively.
D007611:Aprotinin / Q000378:metabolism*; D001665:Binding Sites; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics; D014357:Trypsin / Q000378:metabolism*; D014867:Water
D014867:Water; D007611:Aprotinin; D014357:Trypsin