Inhibition of peptidoglycan biosynthesis by ramoplanin

Somner, Elizabeth A.; Reynolds, Peter E.

doi:10.1128/aac.34.3.413

Cited by 139 publications

(109 citation statements)

References 22 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Ramoplanin factor A2 is currently under Phase III clinical development for eradication of VRE and MRSA. No cases of clinical or laboratory-generated resistance to this antibiotic have been reported (12,13).…”

mentioning

confidence: 99%

“…Reynolds and Somner determined that ramoplanin arrests cell wall biosynthesis at a late stage peptidoglycan (PG) biosynthesis step whereby the enzyme MurG catalyzes the conversion of undecaprenyl-pyrophosphoryl-Nacetylmuramyl-pentapeptide (Lipid I) and uridyl-pyrophosphoryl-N-acetylglucosamine (UDP-GlcNAc) to uridyl-diphosphate (UDP) and undecaprenyl-pyrophosphoryl-N-acetylmuramyl(Nacetylglucoseamine)-pentapeptide (Lipid II) (13). Reynolds further postulated that this mechanism of inhibition might involve complexation of Lipid I by ramoplanin, a mechanism that echoes the mode of action of both glycopeptide antibiotics and select lantibiotics.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: Minimal structural requirements for intermolecular complexation and fibril formation

Čudić

Kranz

Behenna

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

mentioning

confidence: 99%

mentioning

confidence: 99%

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: Minimal structural requirements for intermolecular complexation and fibril formation

Čudić

Kranz

Behenna

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…Lipid II sequestration precludes formation of the mature, fully cross-linked peptidoglycan, leading to a mechanically weakened cell wall and bacterial death from osmotic lysis (11)(12)(13)(14). Thus, like the glycopeptide antibiotics, ramoplanin inhibits cell wall biosynthesis, but the molecular underpinnings are distinct, since the binding epitopes on Lipid II that are recognized by the two types of antibiotics are largely non-overlapping (3,4,10,15,16). This differential targeting likely explains ramoplanin's excellent activity against vancomycin-resistant microorganisms.…”

mentioning

confidence: 99%

“…1). Ramoplanin A2 is highly effective against MRSA and vancomycin-resistant E. faecium (VRE) (3,4) and has recently been in development for the treatment of Clostridium difficile infections. Since the antibiotic's discovery over two decades ago, no clinical or laboratorygenerated resistance to ramoplanin A2 has been reported.…”

mentioning

confidence: 99%

A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface

Hamburger

Hoertz

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The glycodepsipeptide antibiotic ramoplanin A2 is in late stage clinical development for the treatment of infections from Grampositive pathogens, especially those that are resistant to first line antibiotics such as vancomycin. Ramoplanin A2 achieves its antibacterial effects by interfering with production of the bacterial cell wall; it indirectly inhibits the transglycosylases responsible for peptidoglycan biosynthesis by sequestering their Lipid II substrate. Lipid II recognition and sequestration occur at the interface between the extracellular environment and the bacterial membrane. Therefore, we determined the structure of ramoplanin A2 in an amphipathic environment, using detergents as membrane mimetics, to provide the most physiologically relevant structural context for mechanistic and pharmacological studies. We report here the X-ray crystal structure of ramoplanin A2 at a resolution of 1.4 Å. This structure reveals that ramoplanin A2 forms an intimate and highly amphipathic dimer and illustrates the potential means by which it interacts with bacterial target membranes. The structure also suggests a mechanism by which ramoplanin A2 recognizes its Lipid II ligand.glycolipodepsipeptide ͉ mechanism ͉ vancomycin resistance

show abstract

“…microorganism, is a glycolipodepsipeptide antibiotic active against Gram-positive bacteria [6,7]. It comprises a complex of three factors, A1, A2 and A3, which are closely related structurally.…”

Section: Introductionmentioning

confidence: 99%

Retention of native‐like structure in an acyclic counterpart of a β‐sheet antibiotic

1993

View full text Add to dashboard Cite

An acyclic derivative of the cyclic peptide antibiotic, ramoplanin, has been prepared. In aqueous solution, two-dimensional NMR spectroscopy indicates that the acyclic form adopts a threshold population of conformers in which at least part of the fl-sheet characteristic of the intact ramoplanin persists. Thus, despite losing the entropic benefit which the macrocycle must lend to fl-sheet formation, the polypeptide chain of the acyclic ramoplanin appears to display an innate tendency to adopt a native-like conformation.

show abstract

Inhibition of peptidoglycan biosynthesis by ramoplanin

Cited by 139 publications

References 22 publications

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: Minimal structural requirements for intermolecular complexation and fibril formation

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: Minimal structural requirements for intermolecular complexation and fibril formation

A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface

Retention of native‐like structure in an acyclic counterpart of a β‐sheet antibiotic

Contact Info

Product

Resources

About