Cytosolic thymidine kinase 1, TK1, is a well known cell-cycleregulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs such as 3-azido-3-deoxythymidine (AZT). We have now determined the structures of the TK1 family, the human and Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor dTTP. The TK1s have a tetrameric structure in which each subunit contains an ␣͞-domain that is similar to ATPase domains of members of the RecA structural family and a domain containing a structural zinc. The zinc ion connects -structures at the root of a -ribbon that forms a stem that widens to a lasso-type loop. The thymidine of dTTP is hydrogen-bonded to main-chain atoms predominantly coming from the lasso loop. This binding is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin.crystal structures ͉ deoxynucleotide metabolism ͉ prodrug activation
The diffusion of amino acids in aqueous solution was investigated experimentally by a holographic interferometric technique where the real-time holographic interference fringes indicating the concentration profiles of the liquid were obtained by an automatic photographing and memorizing program. The reliability of the instrument was verified by the measurement of the diffusion coefficient of KCl and sucrose in aqueous solution at 298.15 K. Furthermore, the diffusion coefficients of glycine, L-alanine, L-valine, L-isoleucine, L-serine, L-threonine, and L-arginine in aqueous solution at 298.15 K were measured, and the affecting factors of molecular structure and polarity were analyzed and discussed. In addition, on the basis of the Gordon model of the diffusion coefficient in the literature, a new semiempirical model was proposed to predict the liquid diffusion coefficients of amino acids in aqueous solutions. The equation parameters were fitted by the experimental data of seven amino acids in this work and four in the literature.
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