3run

New strategy to analyze structures of glycopeptide antibiotic-target complexes

spinqualitylabelsall models 3run, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3run is a 2 chain structure with sequence from Amycolatopsis orientalis and Escherichia virus T4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 3FG, BGC, CCS, CL, DAL, GHP, IPA, MLU, MPD, MRD, OMY, OMZ, PO4, PRD_000204, RER, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer. Publication Abstract from PubMed Many large natural product antibiotics act by specifically binding and sequestering target molecules found on bacterial cells. We have developed a new strategy to expedite the structural analysis of such antibiotic-target complexes, in which we covalently link the target molecules to carrier proteins, and then crystallize the entire carrier-target-antibiotic complex. Using native chemical ligation, we have linked the Lys-D-Ala-D-Ala binding epitope for glycopeptide antibiotics to three different carrier proteins. We show that recognition of this peptide by multiple antibiotics is not compromised by the presence of the carrier protein partner, and use this approach to determine the first-ever crystal structure for the new therapeutic dalbavancin. We also report the first crystal structure of an asymmetric ristocetin antibiotic dimer, as well as the structure of vancomycin bound to a carrier-target fusion. The dalbavancin structure reveals an antibiotic molecule that has closed around its binding partner; it also suggests mechanisms by which the drug can enhance its half-life by binding to serum proteins, and be targeted to bacterial membranes. Notably, the carrier protein approach is not limited to peptide ligands such as Lys-D-Ala-D-Ala, but is applicable to a diverse range of targets. This strategy is likely to yield structural insights that accelerate new therapeutic development. A carrier protein strategy yields the structure of dalbavancin.,Economou NJ, Nahoum V, Weeks SD, Grasty KC, Zentner IJ, Townsend TM, Bhuiya MW, Cocklin S, Loll PJ J Am Chem Soc. 2012 Mar 14;134(10):4637-45. Epub 2012 Mar 1. PMID:22352468 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lysozyme 3D structures

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