Work

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

Year: 2014

Type: article

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.

Source: The Journal of Organic Chemistry

DOI: 10.1021/jo501625f

Authors: Sunkyu Han, Binh V. Le, Holly S. Hajare, Richard H. G. Baxter, Scott J. Miller

Institution: Yale University

Language: English

Topic: Biochemical and Structural Characterization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: National Institute of General Medical Sciences