Chapter 6 Biochemistry of the penicilloyl serine transferases

Publisher Summary This chapter discusses the biochemistry of the penicilloyl serine transferases. The penicilloyl serine transferases catalyze cleavage of the cyclic amide bond of penicillin via formation of a serine S* ester-linked penicilloyl enzyme. A mechanistic model of the putative peptidase ancestor is provided by the DD-transpeptidase/PBP of Streptomyces K15. Upon cleavage of the signal peptide of the precursor, the exported 262 amino acid residue protein remains in interaction with the outer face of the membrane. The enzyme consists of one catalytic module. The enzyme has been overexpressed and crystallized in a form suitable for X-ray analysis. Features of evolution also resulted in the emergence of distinct classes of DD-peptidases/PBPs, and β-lactamases. Enzymes belonging to a given class are related in their primary structures by similarity scores which are at least five standard deviations above that expected for a run of twenty randomized pairs of proteins having the same amino acid compositions as the pairs of enzymes under comparison.