3f0t

Crystal structure of thymidine kinase from Herpes simplex virus type 1 in complex with N-methyl-DHBT

spinqualitylabelsall models 3f0t, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3f0t is a 2 chain structure with sequence from Human alphaherpesvirus 1 strain 17. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: NCV, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KITH_HHV11 In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to "gold standard" 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K(m) = 10 +/- 0.3 muM; k(cat) = 0.036 +/- 0.015 sec(-1)). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues. Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo.,Martic M, Pernot L, Westermaier Y, Perozzo R, Kraljevic TG, Kristafor S, Raic-Malic S, Scapozza L, Ametamey S Nucleosides Nucleotides Nucleic Acids. 2011 Apr;30(4):293-315. PMID:21623543 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidine kinase 3D structures

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