3p97 | pdb_00003p97

Dengue 3 NS5 Methyltransferase bound to the substrate S-Adenosyl methionine

spinqualitylabelsall models 3p97, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3p97 is a 2 chain structure with sequence from Dengue virus 3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAM Related: 3p8z Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Crystal structure analysis of Flavivirus methyltransferases uncovered a flavivirus-conserved cavity located next to the binding site for its cofactor, S-adenosyl-methionine (SAM). Chemical derivatization of S-adenosyl-homocysteine (SAH), the product inhibitor of the methylation reaction, with substituents that extend into the identified cavity, generated inhibitors that showed improved and selective activity against dengue virus methyltransferase (MTase), but not related human enzymes. Crystal structure of dengue virus MTase with a bound SAH derivative revealed that its N6-substituent bound in this cavity and induced conformation changes in residues lining the pocket. These findings demonstrate that one of the major hurdles for the development of methyltransferase-based therapeutics, namely selectivity for disease-related methyltransferases, can be overcome. Small molecule inhibitors that selectively block dengue virus methyltransferase.,Lim SP, Sonntag LS, Noble C, Nilar SH, Ng RH, Zou G, Monaghan P, Chung KY, Dong H, Liu B, Bodenreider C, Lee G, Ding M, Chan WL, Wang G, Jian YL, Chao AT, Lescar J, Yin Z, Vedananda TR, Keller TH, Shi PY J Biol Chem. 2011 Feb 25;286(8):6233-40. Epub 2010 Dec 8. PMID:21147775 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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