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The ubiquitin-activating enzyme E1 EC 6.3.2.19 represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier proteins E2, ubiquitin-protein ligases E3 and proteins. This process is rather complex, and known from the work of Haas, Ciechanover, Hershko, Rose and others. The occurrence of 19 hypothetical intermediate enzyme forms EFs and 22 different reactions were considered in the presence of ubiquitin Ub, ATP, adenosine 5’-tetraphosphate p4A, pyrophosphate P2, and tripolyphosphate P3 as substrates, and iodoacetamide IAA and dithioth-reitol DTT as inhibitors. Inspired by the work of Cha Cha 1968 J. Biol. Chem., 243, 820-825 we have treated these reactions in two complementary ways: in rapid equilibrium and in steady state. The kinetics of both types of reactions were simulated and solved with a system of ordinary differential equations using the Mathematica Program. The ubiquitination of E1 has been also theoretically coupled to the ubiquitination of E2, E3 and proteins. This makes the model useful to predict the theoretical influence of inhibitors or of changes in some parameters of the reaction on the ubiquitination of proteins. The Program responds to changes in the concentration of ATP or ubiquitin and has predictive properties as shown by the influence of AMP on the synthesis of p4A, calculated theoretically and confirmed experimentally.

KEYWORDS

Dinucleoside Polyphosphates; Adenosine Tetraphosphate; Tripolyphosphate; Proteasome; Mathematical Model

Cite this paper

López-Cánovas, F. , Cánovas, F. , Sillero, M. and Sillero, A. 2010 Mathematical model for the ubiquitin activating enzyme E1. Journal of Biomedical Science and Engineering, 3, 274-284. doi: 10.4236-jbise.2010.33037.





Author: Francisco Javier López-Cánovas, Francisca Cánovas, María Antonia Günther Sillero, Antonio Sillero

Source: http://www.scirp.org/



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