4e5e

Crystal structure of avian influenza virus PAn Apo

spinqualitylabelsall models 4e5e, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4e5e is a 4 chain structure with sequence from Influenza A virus (A/Viet Nam/1203/2004(H5N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [Q5EP34_9INFA] Publication Abstract from PubMed Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or "snatched" from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors. Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease.,Dubois RM, Slavish PJ, Baughman BM, Yun MK, Bao J, Webby RJ, Webb TR, White SW PLoS Pathog. 2012 Aug;8(8):e1002830. Epub 2012 Aug 2. PMID:22876176 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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