Learn More
Although fluorination of pharmacologically active compounds has long been a common strategy to increase their metabolic stability and membrane permeation, the functionality of protein-ligand interactions involving fluorine atoms (fluorine bonding) was only recently recognized in the chemistry and biology communities. In this study, the geometric(More)
Histone deacetylases (HDACs) enzyme is a promising target for the development of anticancer drugs. The enzyme-bound conformation of Trichostatin A (TSA) (PDB ID:1C3R) as an inhibitor of HDACs was used to manually construct a pharmacophore model. This model was then successfully used to identify the bioactive conformation and align flexible and structurally(More)
As a serine/threonine protein kinase, glycogen synthase kinase 3β (GSK3β) is an essential component of several cellular processes, including insulin, growth factor, and Wnt signaling. The conserved K85 is important to GSK3β activity and FRATide binding. To elucidate the mechanisms concerning kinase inactivation and nonbinding of FRATide to GSK3β, molecular(More)
Glycogen synthase kinase 3beta (GSK 3beta) is a key component of several cellular processes including Wnt and insulin signalling pathways. The interaction of GSK3beta with scaffolding peptide axin is thought to be responsible for the effective phosphorylation of beta-catenin, the core effector of Wnt signaling, which has been linked with the occurrence of(More)
Many Ser/Thr protein kinases, to be fully activated, are obligated to introduce a phospho-Ser/Thr in their activation loop. Presently, the similarity of activation loop between two crystal complexes, i.e. glycogen synthase kinase 3beta (GSK3beta)-AMPNP and GSK3beta-sulfate ion complex, indicates that the activation segment of GSK3beta is preformed requiring(More)
The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T-cell activation. It contains a sterile-alpha motif (SAM) domain, 3 phosphotyrosine motifs, a proline-rich region, and a Src homology 2 domain. Whereas the other domains have been extensively(More)
Macrophage migration inhibitory factor (MIF) exhibits tautomerase activity on phenylpyruvate and has E-stereochemistry preference. To investigate the binding modes of its competitive inhibitors and evaluate their binding affinities, molecular dynamics simulations together with MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) analysis were(More)
A new method is described to measure the geometric similarity between protein-RNA interfaces quantitatively. The method is based on a procedure that dissects the interface geometry in terms of the spatial relationships between individual amino acid nucleotide pairs. Using this technique, we performed an all-on-all comparison of 586 protein-RNA interfaces(More)
Phospholipase D (PLD) proteins are enzymes that catalyze the hydrolysis of phosphatidylcholine to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a putative second messenger implicated in the regulation of vesicular trafficking and cytoskeletal reorganization. Previous studies using inhibitors and overexpression of PLD(More)
A comparative molecular field analysis (CoMFA) of alkanoic acid 3-oxo-cyclohex-1-enyl ester and 2-acylcyclohexane-1,3-dione derivatives of 4-hydroxyphenylpyruvate dioxygenase inhibitors has been performed to determine the factors required for the activity of these compounds. The substrate's conformation abstracted from dynamic modeling of the(More)