The Role of Substrate Structure in Recognition and Regulation of Enzymatic Interconversion of Proteins

Abstract

Enzyme-catalyzed covalent modification of proteins requires a specialized catalyst that preferentially interacts with a defined region of the protein substrate. The nature of this interaction is of considerable biological significance, as enzyme-catalyzed chemical modification of proteins, primarily enzymes, is a fundamental mechanism by which cellular activities are controlled. Proteins can be characterized by four orders of structure; the contribution that each order of structure plays in the architecture of a site recognized by a modifying enzyme is difficult to assess. Although primary structure determines the remaining structures, substrates of enzymes which glycosylate asparagine, hydroxylate proline, or lysine, and phosphorylate serine/threonine or tyrosine residue contain one or more particular amino acids in common near the modified residue. The adenylylation of Escherichia coli glutamine synthetase appears to represent a type of enzyme interconversion in which substrate tertiary or quaternary structural elements are essential for covalent modification. The phosphorylation and dephosphorylation of skeletal muscle glycogen phosphorylase illustrate several aspects of the involvement of different levels of substrate structure on enzyme interconversion. The phosphorylation–dephosphorylation of phosphorylase at a unique serine residue is a key regulatory mechanism for controlling glycogen metabolism in this tissue.