X-ray crystal structure of teicoplanin A₂-2 bound to a catalytic peptide sequence via the carrier protein strategy.
Publication Type:
Journal ArticleSource:
J Org Chem, Volume 79, Issue 18, p.8550-6 (2014)Keywords:
Acetylglucosamine, Amino Acid Sequence, Anti-Bacterial Agents, Binding Sites, Carrier Proteins, Catalysis, Crystallography, X-Ray, Molecular Conformation, Phosphorylation, TeicoplaninAbstract:
<p>We report the X-ray crystal structure of a site-selective 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 N-acetylglucosamine 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 N-acetylglucosamine 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. </p>