on the conservation of the slow conformational dynamics within the amino acid kinase family nagk the paradigm中的构象变化缓慢的保护氨基酸激酶家族nagk范例.pdfVIP

On the Conservation of the Slow Conformational Dynamics within the Amino Acid Kinase Family: NAGK the Paradigm 1 1 2 Enrique Marcos , Ramon Crehuet *, Ivet Bahar * 1 Department of Biological Chemistry and Molecular Modelling, IQAC-CSIC, Barcelona, Spain, 2 Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Abstract N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequenceRstruc- tureRdynamicsRfunction. Citation: Marcos E, Crehuet R, Bahar I (2010) On the Conservation of the Slow Conformational Dynamics within the Amino Acid Kinase Family: NAGK the Paradigm. PLoS Comput Biol 6(4): e1000738. doi:10.1371/journal.pcbi.1000738 Editor: Michael Levitt, Stanford University, United States of America Received November 2