In previous research, through measurement of torsional values in Protein Data Bank files of enzyme/protein inhibitor complexes and averaging those values to achieve a mean conformation, subtilisin and trypsin were found to favor extensive alignments of atomic orbitals in their active-serine-bearing strand and in the bound inhibitor strand. It was also shown that long oligopeptide esters are significantly more reactive under non-enzymatic acyl-transfer conditions than short ones. Now, corresponding chymotrypsin complexes have been analyzed similarly and found to have extensive orbital alignments similar to those of both systems. Seven files of chymotrypsin/inhibitor complexes were analyzed; the selected files were all of resolutions at or below 2.5 angstroms to favor the quality of the results. As with the subtilisin system, the mean conformation of the bound inhibitor shows orbital alignments from the P2’ to P4 positions. Four extensive alignments of orbitals are evident from the research. The alignments are located in the following places: upstream and downstream of the targeted linkage in the enzyme-bound loop, from serine 195 to glycine 196, and from serine 195 to proline 198. All four alignments converge at the targeted linkage of the bound strand. These orbital alignments may help to induce and optimize the charge dynamics of acyl-transfer during proteolysis. If they serve that role, it would also be consistent with the known kinetic substrate-length dependences of all three enzymes. This research and the previous results suggest that there is a kinetic benefit for enzymes and substrates to engage in orbital alignments during proteolysis. The breadth of these findings predicts that such orbital alignments will also be present in other kinds of enzyme/ligand complexes.

Intramolecular orbital alignments in the active site of chymotrypsin/protein inhibitor complexes

ACS Spring Meeting 2021

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