D-Ala-D-Ala carboxypeptidase VanY

This chapter elaborates the structural chemistry and the biological aspects of D-Ala-D-Ala carboxypeptidase vanY gene. The 909 bp vanY gene encodes a 303-residue protein of 34,980 Da. The predicted amino acid sequence does not contain the SXXK motif common to serine-type DD-carboxypeptidases, consistent with the lack of reactivity with β-lactam antibiotics. There is also no significant sequence similarity with the zinc-dependent DD-carboxypeptidase from Streptomyces albus. Thus, vanY appears to belong to a novel class of DD-carboxypeptidases. The active site of D-Ala-D-Ala dipeptidase vanX has been explored in detail. Sequence analysis predicts that vanY should have an active site and mechanism of action very similar to vanX. The association of inducible DD-carboxypeptidase activity with vancomycin resistance in enterococci suggested an intimate relationship between this activity and drug resistance. The realization that vanY was not required for high-level vancomycin resistance but that vanY gene was located immediately downstream from vanX and under control of the positively regulated PvanH promoter suggested a more subtle association between vanY and vancomycin resistance phenotype.