6b88

E. coli LepB in complex with GNE0775 ((4S,7S,10S)-10-((S)-4-amino-2-(2-(4-(tert-butyl)phenyl)-4-methylpyrimidine-5-carboxamido)-N-methylbutanamido)-16,26-bis(2-aminoethoxy)-N-(2-iminoethyl)-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxamide)E. coli LepB in complex with GNE0775 ((4S,7S,10S)-10-((S)-4-amino-2-(2-(4-(tert-butyl)phenyl)-4-methylpyrimidine-5-carboxamido)-N-methylbutanamido)-16,26-bis(2-aminoethoxy)-N-(2-iminoethyl)-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxamide)

Structural highlights 6b88 is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.407Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEP_ECOLI Publication Abstract from PubMed Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts no new class of antibiotic with activity against Gram-negative bacteria has been approved in over fifty years. Natural products and their derivatives have a key role in combating Gram-negative pathogens. Here we report chemical optimization of the arylomycins-a class of natural products with weak activity and limited spectrum-to obtain G0775, a molecule with potent, broad-spectrum activity against Gram-negative bacteria. G0775 inhibits the essential bacterial type I signal peptidase, a new antibiotic target, through an unprecedented molecular mechanism. It circumvents existing antibiotic resistance mechanisms and retains activity against contemporary multidrug-resistant Gram-negative clinical isolates in vitro and in several in vivo infection models. These findings demonstrate that optimized arylomycin analogues such as G0775 could translate into new therapies to address the growing threat of multidrug-resistant Gram-negative infections. Optimized arylomycins are a new class of Gram-negative antibiotics.,Smith PA, Koehler MFT, Girgis HS, Yan D, Chen Y, Chen Y, Crawford JJ, Durk MR, Higuchi RI, Kang J, Murray J, Paraselli P, Park S, Phung W, Quinn JG, Roberts TC, Rouge L, Schwarz JB, Skippington E, Wai J, Xu M, Yu Z, Zhang H, Tan MW, Heise CE Nature. 2018 Sep;561(7722):189-194. doi: 10.1038/s41586-018-0483-6. Epub 2018 Sep, 12. PMID:30209367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6b88, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image