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Cocktailed fragment screening by X-ray crystallography of the antibacterial target undecaprenyl pyrophosphate synthase from Acinetobacter baumannii

DOI: 10.1107/S2053230X19017199 DOI Help

Authors: James H. Thorpe (GSK Medicines Research Centre) , Ian D. Wall (GSK Medicines Research Centre) , Robert H. Sinnamon (GlaxoSmithKline) , Amy N. Taylor (GlaxoSmithKline) , Robert A. Stavenger (GlaxoSmithKline)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 76 , PAGES 40 - 46

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 5799

Abstract: Direct soaking of protein crystals with small-molecule fragments grouped into complementary clusters is a useful technique when assessing the potential of a new crystal system to support structure-guided drug discovery. It provides a robustness check prior to any extensive crystal screening, a double check for assay binding cutoffs and structural data for binding pockets that may or may not be picked out in assay measurements. The structural output from this technique for three novel fragment molecules identified to bind to the antibacterial target Acinetobacter baumannii undecaprenyl pyrophosphate synthase are reported, and the different physicochemical requirements of a successful antibiotic are compared with traditional medicines.

Journal Keywords: undecaprenyl pyrophosphate synthase; fragment screening; Acinetobacter baumannii

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)