Thu, 21 Aug 2008 14:13:12 BST CiteULike: tny's Xia http://www.citeulike.org/user/tny/author/Xia CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/tny/article/1016800 <i>Science, Vol. 314, No. 5807. (22 December 2006), pp. 1938-1941.</i><br /><br />Most studies of protein networks operate on a high level of abstraction, neglecting structural and chemical aspects of each interaction. Here, we characterize interactions by using atomic-resolution information from three-dimensional protein structures. We find that some previously recognized relationships between network topology and genomic features (e.g., hubs tending to be essential proteins) are actually more reflective of a structural quantity, the number of distinct binding interfaces. Subdividing hubs with respect to this quantity provides insight into their evolutionary rate and indicates that additional mechanisms of network growth are active in evolution (beyond effective preferential attachment through gene duplication). Relating three-dimensional structures to protein networks provides evolutionary insights. PM Kim LJ Lu Y Xia MB Gerstein doi:10.1126/science.1136174 Science, Vol. 314, No. 5807. (22 December 2006), pp. 1938-1941. 2006-12-27T12:42:51-00:00 2006 Science 1095-9203 314 5807 1938 1941 network structure http://www.citeulike.org/user/tny/article/1165109 <i>Archives of Biochemistry and Biophysics, Vol. 433, No. 1. (1 January 2005), pp. 129-143.</i><br /><br />Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates linked to other moieties, X, and contain the sequence motif or Nudix box, GX5EX7REUXEEXGU. The mechanisms of Nudix hydrolases are highly diverse in the position on the substrate at which nucleophilic substitution occurs, and in the number of required divalent cations. While most proceed by associative nucleophilic substitutions by water at specific internal phosphorus atoms of a diphosphate or polyphosphate chain, members of the GDP-mannose hydrolase sub-family catalyze dissociative nucleophilic substitutions, by water, at carbon. The site of substitution is likely determined by the positions of the general base and the entering water. The rate accelerations or catalytic powers of Nudix hydrolases range from 109- to 1012-fold. The reactions are accelerated 103-105-fold by general base catalysis by a glutamate residue within, or beyond the Nudix box, or by a histidine beyond the Nudix box. Lewis acid catalysis, which contributes [greater-or-equal, slanted]103-105-fold to the rate acceleration, is provided by one, two, or three divalent cations. One divalent cation is coordinated by two or three conserved residues of the Nudix box, the initial glycine and one or two glutamate residues, together with a remote glutamate or glutamine ligand from beyond the Nudix box. Some Nudix enzymes require one (MutT) or two additional divalent cations (Ap4AP), to neutralize the charge of the polyphosphate chain, to help orient the attacking hydroxide or oxide nucleophile, and/or to facilitate the departure of the anionic leaving group. Additional catalysis (10-103-fold) is provided by the cationic side chains of lysine and arginine residues and by H-bond donation by tyrosine residues, to orient the general base, or to promote the departure of the leaving group. The overall rate accelerations can be explained by both independent and cooperative effects of these catalytic components. Structures and mechanisms of Nudix hydrolases AS Mildvan Z Xia HF Azurmendi V Saraswat PM Legler MA Massiah SB Gabelli MA Bianchet LW Kang LM Amzel doi:10.1016/j.abb.2004.08.017 Archives of Biochemistry and Biophysics, Vol. 433, No. 1. (1 January 2005), pp. 129-143. 2007-03-15T08:59:02-00:00 2005 Archives of Biochemistry and Biophysics 433 1 129 143 catalytic_mechanism enzyme_superfamily review