8t5w

Influenza PAN endonuclease I38T mutant with Baloxavir

spinqualitylabelsall models 8t5w, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8t5w is a 1 chain structure with sequence from Influenza A virus (A/California/04/2009(H1N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: E4Z, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Vital to the treatment of influenza is the use of antivirals such as Oseltamivir (Tamiflu) and Zanamivir (Relenza); however, antiviral resistance is becoming an increasing problem for these therapeutics. The RNA-dependent RNA polymerase acidic N-terminal (PA(N)) endonuclease, a critical component of influenza viral replication machinery, is an antiviral target that was recently validated with the approval of Baloxavir Marboxil (BXM). Despite its clinical success, BXM has demonstrated susceptibility to resistance mutations, specifically the I38T, E23K, and A36 V mutants of PA(N). To better understand the effects of these mutations on BXM resistance and improve the design of more robust therapeutics, this study examines key differences in protein-inhibitor interactions with two inhibitors and the I38T, E23K, and A36 V mutants. Differences in inhibitor binding were evaluated by measuring changes in binding to PA(N) using two biophysical methods. The binding mode of two distinct inhibitors was determined crystallographically with both wild-type and mutant forms of PA(N). Collectively, these studies give some insight into the mechanism of antiviral resistance of these mutants. Structural Studies of Inhibitors with Clinically Relevant Influenza Endonuclease Variants.,Kohlbrand AJ, Stokes RW, Sankaran B, Cohen SM Biochemistry. 2024 Feb 6;63(3):264-272. doi: 10.1021/acs.biochem.3c00536. Epub , 2024 Jan 8. PMID:38190441 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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