| Structural highlights
6b89 is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | lptB, yhbG, b3201, JW3168 (ECOLI) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[LPTB_ECOLI] Part of the ABC transporter complex LptBFG involved in the translocation of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. Probably responsible for energy coupling to the transport system.[1] [2] [3]
Publication Abstract from PubMed
Novobiocin is an orally active antibiotic that inhibits DNA gyrase by binding the ATP-binding site in the ATPase subunit. Although effective against Gram-positive pathogens, novobiocin has limited activity against Gram-negative organisms due to the presence of the lipopolysaccharide-containing outer membrane, which acts as a permeability barrier. Using a novobiocin-sensitive Escherichia coli strain with a leaky outer membrane, we identified a mutant with increased resistance to novobiocin. Unexpectedly, the mutation that increases novobiocin resistance was not found to alter gyrase, but the ATPase that powers lipopolysaccharide (LPS) transport. Co-crystal structures, biochemical, and genetic evidence show novobiocin directly binds this ATPase. Novobiocin does not bind the ATP binding site but rather the interface between the ATPase subunits and the transmembrane subunits of the LPS transporter. This interaction increases the activity of the LPS transporter, which in turn alters the permeability of the outer membrane. We propose that novobiocin will be a useful tool for understanding how ATP hydrolysis is coupled to LPS transport.
The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport.,May JM, Owens TW, Mandler MD, Simpson BW, Lazarus MB, Sherman DJ, Davis RM, Okuda S, Massefski W, Ruiz N, Kahne D J Am Chem Soc. 2017 Nov 22. doi: 10.1021/jacs.7b07736. PMID:29135241[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sperandeo P, Pozzi C, Deho G, Polissi A. Non-essential KDO biosynthesis and new essential cell envelope biogenesis genes in the Escherichia coli yrbG-yhbG locus. Res Microbiol. 2006 Jul-Aug;157(6):547-58. Epub 2006 Feb 9. PMID:16765569 doi:10.1016/j.resmic.2005.11.014
- ↑ Sperandeo P, Cescutti R, Villa R, Di Benedetto C, Candia D, Deho G, Polissi A. Characterization of lptA and lptB, two essential genes implicated in lipopolysaccharide transport to the outer membrane of Escherichia coli. J Bacteriol. 2007 Jan;189(1):244-53. Epub 2006 Oct 20. PMID:17056748 doi:http://dx.doi.org/10.1128/JB.01126-06
- ↑ Sperandeo P, Lau FK, Carpentieri A, De Castro C, Molinaro A, Deho G, Silhavy TJ, Polissi A. Functional analysis of the protein machinery required for transport of lipopolysaccharide to the outer membrane of Escherichia coli. J Bacteriol. 2008 Jul;190(13):4460-9. Epub 2008 Apr 18. PMID:18424520 doi:JB.00270-08
- ↑ May JM, Owens TW, Mandler MD, Simpson BW, Lazarus MB, Sherman DJ, Davis RM, Okuda S, Massefski W, Ruiz N, Kahne D. The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport. J Am Chem Soc. 2017 Nov 22. doi: 10.1021/jacs.7b07736. PMID:29135241 doi:http://dx.doi.org/10.1021/jacs.7b07736
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