4nam

1.7A structure of 5-Fluoro Tryptophan Labeled Protective Antigen (W206Y)

spinqualitylabelsall models 4nam, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4nam is a 1 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, FTR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAG_BACAN One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. Publication Abstract from PubMed The anthrax protective antigen (PA) is an 83 kDa protein that is one of three protein components of the anthrax toxin, an AB toxin secreted by Bacillus anthracis. PA is capable of undergoing several structural changes, including oligomerization to either a heptameric or octameric structure called the prepore, and at acidic pH a major conformational change to form a membrane-spanning pore. To follow these structural changes at a residue-specific level, we have conducted initial studies in which we have biosynthetically incorporated 5-fluorotryptophan (5-FTrp) into PA, and we have studied the influence of 5-FTrp labeling on the structural stability of PA and on binding to the host receptor capillary morphogenesis protein 2 (CMG2) using 19F nuclear magnetic resonance (NMR). There are seven tryptophans in PA, but of the four domains in PA, only two contain tryptophans: domain 1 (Trp65, -90, -136, -206, and -226) and domain 2 (Trp346 and -477). Trp346 is of particular interest because of its proximity to the CMG2 binding interface, and because it forms part of the membrane-spanning pore. We show that the 19F resonance of Trp346 is sensitive to changes in pH, consistent with crystallographic studies, and that receptor binding significantly stabilizes Trp346 to both pH and temperature. In addition, we provide evidence that suggests that resonances from tryptophans distant from the binding interface are also stabilized by the receptor. Our studies highlight the positive impact of receptor binding on protein stability and the use of 19F NMR in gaining insight into structural changes in a high-molecular weight protein. F Nuclear Magnetic Resonance and Crystallographic Studies of 5-Fluorotryptophan-Labeled Anthrax Protective Antigen and Effects of the Receptor on Stability.,Chadegani F, Lovell S, Mullangi V, Miyagi M, Battaile KP, Bann JG Biochemistry. 2014 Jan 15. PMID:24387629 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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