Work

Desleucyl-Oritavancin with a Damaged d -Ala- d -Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus

Year: 2017

Type: article

Abstract: We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus . Measurements performed on whole cells labeled selectively in vivo have established that des- N -methylleucyl- N -4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [ 19 F]oritavancin, which has a damaged d -Ala- d -Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs.

Source: Biochemistry

DOI: 10.1021/acs.biochem.6b01125

Authors: Sung Joon Kim, Manmilan Singh, Shasad Sharif, Jacob Schaefer

Institutions: Baylor University, Washington University in St. Louis

Language: English

Topic: Antimicrobial Resistance in Staphylococcus

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of General Medical Sciences