6gn7

X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.

spinqualitylabelsall models 6gn7, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gn7 is a 3 chain structure with sequence from Homo sapiens 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 2.8Å Ligands: 0G6, BMA, GAL, GOL, MAN, NA, NAG, SIA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Despite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties. Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer.,Troisi R, Napolitano V, Spiridonova V, Russo Krauss I, Sica F Nucleic Acids Res. 2018 Oct 24. pii: 5144158. doi: 10.1093/nar/gky990. PMID:30357392 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thrombin 3D Structures

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