Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH.
Journal, issue, pages	Nat Commun, Vol. 16, Issue 1, Page 3224, Year 2025
Publish date	Apr 4, 2025
Authors	Franco K K Li / Shaun C Peters / Liam J Worrall / Tianjun Sun / Jinhong Hu / Marija Vuckovic / Maya Farha / Armando Palacios / Nathanael A Caveney / Eric D Brown / Natalie C J Strynadka /
PubMed Abstract	Wall teichoic acid (WTA) is a polyol phosphate polymer that covalently decorates peptidoglycan of gram-positive bacteria, including Staphylococcus aureus. Central to WTA biosynthesis is flipping of ...Wall teichoic acid (WTA) is a polyol phosphate polymer that covalently decorates peptidoglycan of gram-positive bacteria, including Staphylococcus aureus. Central to WTA biosynthesis is flipping of lipid-linked precursors across the cell membrane by TarGH, a type V ABC transporter. Here, we present cryo-EM structures of S. aureus TarGH in the presence of targocil-II, a promising small-molecule lead with β-lactam antibiotic synergistic action. Targocil-II binds to the extracellular dimerisation interface of TarG, we suggest mimicking flipped but not yet released substrate. In absence of targocil-II and in complex with ATP analogue ATPγS, determined at 2.3 Å resolution, the ATPase active site is allosterically inhibited. This is due to a so far undescribed D-loop conformation, potentially minimizing spurious ATP hydrolysis in the absence of substrate. Targocil-II binding comparatively causes local and remote conformational changes through to the TarH active site, with the D-loop now optimal for ATP hydrolysis. These structures suggest an ability to modulate ATP hydrolysis in a WTA substrate dependent manner and a jammed ATPase cycle as the basis of the observed inhibition by targocil-II. The molecular insights provide an unprecedented basis for development of TarGH targeted therapeutics for treatment of multidrug-resistant S. aureus and other gram-positive bacterial infections.
External links	Nat Commun / PubMed:40185711 / PubMed Central
Methods	EM (single particle)
Resolution	2.3 - 3.02 Å
Structure data	45550 9cfl EMDB-45550, PDB-9cfl: Cryo-EM structure of S. aureus TarGH in complex with ATP-gamma-S Method: EM (single particle) / Resolution: 2.3 Å 45554 9cfp EMDB-45554, PDB-9cfp: Cryo-EM structure of S. aureus TarGH in complex with AMP-PNP and targocil-II Method: EM (single particle) / Resolution: 2.9 Å 48274 9mhd EMDB-48274, PDB-9mhd: Cryo-EM structure of S. aureus TarGH in complex with ATP-gamma-S Method: EM (single particle) / Resolution: 2.92 Å 48281 9mhu EMDB-48281, PDB-9mhu: Cryo-EM structure of S. aureus TarGH in complex with Targocil-II and ATP-gamma-S in a catalytically competent conformation Method: EM (single particle) / Resolution: 3.02 Å 48282 9mhz EMDB-48282, PDB-9mhz: Cryo-EM structure of S. aureus TarGH in complex with Targocil-II and ATP-gamma-S in a catalytically incompetent conformation Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	ChemComp-AV0: Lauryl Maltose Neopentyl Glycol ChemComp-AGS: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogueYM ChemComp-MG: Unknown entry ChemComp-HOH: WATER PDB-1av9: Unknown entry ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogueYM
Source	staphylococcus aureus (bacteria)
Keywords	MEMBRANE PROTEIN / ABC transporter / teichoic acid / bacteria