According to the chemical property of N-phosphoamino acids, we deduce a novel FDA-approved Drug Library concentration three-step covalent mechanism (Ni et al., 2005), which is much different from ‘in-line
phosphorus transfer’ mechanism (Valief et al., 2003). It is known that human contains 518 kinds of protein kinases to regulate the cell’s signal. Among them, more than 80% are the serine, threonine and tyrosine kinases with the hydroxyl group as the receptors phosphotransferases with a alcohol group as acceptor (E.C 2.7.1.X).While in the literature, there are phosphotransferases with a nitrogenous group as acceptor (E.C 2.7.3.X) and phosphotransferases with a carboxyl group as acceptor (E.C 2.7.2.X). Therefore, it might be a reasonable approach to illuminate the kinases catalyzing the phosphoryl transfer mechanism by comparison of these three types of kinases. These three types of Pim inhibitor kinases, catalyze the γ-P of the ATP transfer to their corresponding substrates with three different phosphoryl groups of receptors, namely the HO-receptor, H2N-receptor and the HOOC-receptor (see figure 1). By the thermodynamical data, it seems that the carboxyl mixed anhydride 1, easy to hydrolysis, contain much higher energy than the phosphoamide bond 2 (617 kJ mol−1), which in turn is higher than the phosphoester bond 3 (597 kJ mol−1) (Lange). In this paper,
by the evolution investigation, the Ser/Thr kinases phosphoryl transfer mechanism
might go through the combination Teicoplanin of the P-NH-residues and the P-OOC-residues mechanism. since the key catalytic residues of Ser/Thr kinases are Lys and Asp, it was proposed that the γ-P of the ATP is not directly transfer to the substrate, but might be proceeded by γ-P-Lys and γ-P-Asp high-energy intermediates and then finally phosphorylate the substrate. Lange’s Chemistry Handbook Version 15th. section 4. properties of atoms, radicals, and bonds. Ni, F., et al., Analysis of the phosphoryl transfer mechanism of c-AMP dependent protein kinase (PKA) by penta-coodinate phosphoric transition state theory. Current Protein & Peptide Science, 2005. 6(5): p. 437–442. Valiev, M., et al., The Role of the Putative Catalytic Base in the Phosphoryl Transfer Reaction in a Protein Kinase: First-Principles Calculations. Journal of the American Chemical Society, 2003. 125(33): p. 9926–9927. E-mail: [email protected]edu.cn Precellular Evolution A Trade-Off Between Neutrality and Adaptability Limits the Optimization of Viral Quasispecies Jacobo Aguirre Centro de Astrobiología, INTA-CSIC. Ctra. de Ajalvir km. 4, 28850 Torrejón de Ardoz, Madrid, SPAIN Theoretical studies of quasispecies, concept presented in (Eigen, 1971), usually focus on two properties of those populations at the mutation-selection equilibrium, namely asymptotic growth rate and population diversity.