X-ray crystal structure of teicoplanin A2-2 bound to a catalytic peptide sequence via the carrier protein strategy

Abstract

We report the X-ray crystal structure of a siteselective peptide catalyst moiety and teicoplanin A2-2 complex. The expressed protein ligation technique was used to couple T4 lysozyme (T4L) and a synthetic peptide catalyst responsible for the selective phosphorylation of the Nacetylglucosamine sugar in a teicoplanin A2-2 derivative. The T4L-Pmh-DPro-Aib-DAla-DAla construct was crystallized in the presence of teicoplanin A2-2. The resulting 2.3 Å resolution protein-peptide-teicoplanin complex crystal structure revealed that the nucleophilic nitrogen of N-methylimidazole in the Pmh residue is in closer proximity (7.6 Å) to the Nacetylglucosamine than the two other sugar rings present in teicoplanin (9.3 and 20.3 Å, respectively). This molecular arrangement is consistent with the observed selectivity afforded by the peptide-based catalyst when it is applied to a site-selective phosphorylation reaction involving a teicoplanin A2-2 derivative.