title: 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 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.
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06511, United States.
authors.forename: Sunkyu
authors.initials: S
authors.lastname: Han
authors.forename: Binh V
authors.initials: BV
authors.lastname: Le
authors.forename: Holly S
authors.initials: HS
authors.lastname: Hajare
authors.forename: Richard H G
authors.initials: RH
authors.lastname: Baxter
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D002352:Carrier Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D010766:Phosphorylation; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; C000594918:teicoplanin A2; D017334:Teicoplanin; D000117:Acetylglucosamine