E. coli beta-galactosidase is a tetramer of four identical 1023-amino acid chains. Each chain consists of five domains, the third of which is an eight-stranded alpha/beta barrel that comprises much of the active site. This site does, however, include elements from other domains and other subunits. The N-terminal region of the polypeptide chains help form one of the subunit interfaces. Taken together these features provide a structural basis for the well-known property of alpha-complementation. Catalytic activity proceeds via the formation of a covalent galactosyl intermediate with Glu537, and includes 'shallow' and 'deep' modes of substrate binding.