X-ray Crystal Structure of Teicoplanin A2-2 Bound to a Catalytic Peptide Sequence via the Carrier Protein Strategy

We report the X-ray crystal structure of a site-selective peptide catalyst moiety and teicoplanin A(2)-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 N-acetylglucosamine sugar in a teicoplanin A(2)-2 derivative. The T4L-Pmh-DPro-Aib-DAla-DAla construct was crystallized in the presence of teicoplanin A(2)-2. The resulting 2.3 angstrom 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 angstrom) to the N-acetylglucosamine than the two other sugar rings present in teicoplanin (9.3 and 20.3 angstrom, 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 A(2)-2 derivative.