STREPTOMYCES K15 ACTIVE-SITE SERINE DD-TRANSPEPTIDASE - SPECIFICITY PROFILE FOR PEPTIDE, THIOL ESTER AND ESTER CARBONYL DONORS AND PATHWAYSOF THE TRANSFER-REACTIONS

The Streptomyces K15 transferase is a penicillin-binding protein presu med to be involved in bacterial wall peptidoglycan cross-linking. It c atalyses cleavage of the peptide, thiol ester or ester bond of carbony l donors Z-R(1)-CONH-CHR(2)-COX-CHR(3)-COO- (where X is NH, S or O) an d transfers the electrophilic group Z-R(1)-CONH-CHR(2)-CO to amino acc eptors via an acyl-enzyme intermediate. Kinetic data suggest that the amino acceptor behaves as a simple alternative nucleophile at the leve l of the acyl-enzyme in the case of thiol ester and ester donors, and that it binds to the enzyme . carbonyl donor Michaelis complex and inf luences the rate of enzyme acylation by the carbonyl donor in the case of amide donors. Depending on the nature of the scissile bond, the en zyme has different requirements for substituents at positions R(1), R( 2) and R(3).