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We report the 1.7 Å resolution crystal structure of the Lip2 lipase from Yarrowia lipolytica in its closed conformation. The Lip2 structure is highly homologous to known structures of the fungal lipase family (Thermomyces lanuginosa, Rhizopus niveus, and Rhizomucor miehei lipases). However, it also presents some unique features that are described and(More)
Large-scale conformational rearrangement of a lid subdomain is a key event in the interfacial activation of many lipases. We present herein a study in which the large-scale "open-to-closed" movement of Burkholderia cepacia lipase lid has been simulated at the atomic level using a hybrid computational method. The two-stage approach combines path-planning(More)
The specific activity of the human immunodeficiency virus, type 1 (HIV-1), integrase on the viral long terminal repeat requires the binding of the enzyme to certain sequences located in the U3 and U5 regions at the ends of viral DNA, but the determinants of this specific DNA-protein recognition are not yet completely understood. We synthesized DNA duplexes(More)
This paper builds on the combination of robotic path planning algorithms and molecular modeling methods for computing large-amplitude molecular motions, and introduces voxel maps as a computational tool to encode and to represent such motions. We investigate several applications and show results that illustrate the interest of such representation.
Amylosucrases are sucrose-utilizing α-transglucosidases that naturally catalyze the synthesis of α-glucans, linked exclusively through α1,4-linkages. Side products and in particular sucrose isomers such as turanose and trehalulose are also produced by these enzymes. Here, we report the first structural and biophysical characterization of the most(More)
Iterative saturation mutagenesis and combinatorial active site saturation focused on vicinal amino acids were used to alter the acceptor specificity of amylosucrase from Neisseria polysaccharea , a sucrose-utilizing α-transglucosidase, and sort out improved variants. From the screening of three semirational sublibraries accounting in total for 20,000(More)
Styrylquinoline derivatives (SQ) efficiently inhibit the 3'-processing activity of integrase (IN) with IC50 values of between 0.5 and 5 microM. We studied the mechanism of action of these compounds in vitro. First, we used steady-state fluorescence anisotropy to assay the effects of the SQ derivatives on the formation of IN-viral DNA complexes independently(More)
Development of synthetic routes to complex carbohydrates and glyco-conjugates is often hampered by the lack of enzymes with requisite properties or specificities. Indeed, assembly or degradation of carbohydrates requires carbohydrate-active enzymes (CAZymes) able to act on a vast range of glycosidic monomers, oligomers or polymers in a regio-specific or(More)
MOTIVATION The main challenge for structure-based computational protein design (CPD) remains the combinatorial nature of the search space. Even in its simplest fixed-backbone formulation, CPD encompasses a computationally difficult NP-hard problem that prevents the exact exploration of complex systems defining large sequence-conformation spaces. RESULTS(More)