Solution structure determination for the CYS74 to ALA74 mutant of the catalytic domain of Zoocin A

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Zoocin A is a Zn-metallopeptidase secreted by Streptococcus zooepidemicus strain 4881. It has strong inhibitory activity against Streptococcus mutans and thus can serve as a potential treatment for dental caries. The solution NMR structure of the Cys74 to Ala74 mutant of the recombinant catalytic domain (rCAT C74A) of zoocin A has been determined. The structure of rCAT C74A, together with the structure of recombinant target recognition domain (rTRD) of zoocin A, completes a three dimensional view of zoocin A. While the structure of rCAT C74A resembles those of lysostaphin and lytM, the substrate binding groove is wider and no tyrosine residue was observed in the active site. The wider binding groove of rCAT C74A may account for its substrate specificity for D-alanyl-L-alanine peptides, and the absence of a tyrosyl residue or spatially and structurally equivalent hydrogen bond donor in the active site indicates that rCAT C74A may adopt a catalytic mechanism different in some details from that of lytM, and the catalytic mechanism of M23 endopeptidases may have divergent aspects.

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