4wx4

Crystal structure of adenovirus 8 protease in complex with a nitrile inhibitor

spinqualitylabelsall models 4wx4, resolution 1.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wx4 is a 2 chain structure with sequence from Human adenovirus D8 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.03Å Ligands: 3VF, EPE, GLY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B9A5C1_ADE08 Publication Abstract from PubMed Adenoviral infections are associated with a wide range of acute diseases, among which ocular viral conjunctivitis (EKC) and disseminated disease in immunocompromised patients. To date, no approved specific anti-adenoviral drug is available, but there is a growing need for an effective treatment of such infections. The adenoviral protease, adenain, plays a crucial role for the viral lifecycle and thus represents an attractive therapeutic target. Structure-guided design with the objective to depeptidize tetrapeptide nitrile 1 led to the novel chemotype 2. Optimization of scaffold 2 resulted in picomolar adenain inhibitors 3a and 3b. In addition, a complementary series of irreversible vinyl sulfone containing inhibitors were rationally designed, prepared and evaluated against adenoviral protease. High resolution X-ray co-crystal structures of representatives of each series proves the successful design of these inhibitors and provides an excellent basis for future medicinal chemistry optimization of these compounds. Structure-based design and optimization of potent inhibitors of the adenoviral protease.,Grosche P, Sirockin F, Mac Sweeney A, Ramage P, Erbel P, Melkko S, Bernardi A, Hughes N, Ellis D, Combrink KD, Jarousse N, Altmann E Bioorg Med Chem Lett. 2015 Feb 1;25(3):438-43. doi: 10.1016/j.bmcl.2014.12.057., Epub 2014 Dec 24. PMID:25571794 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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