Crystallization of Arthrobacter sp. strain 1C N-(1-D-carboxyethyl)-L-norvaline dehydrogenase and its complex with NAD+

The novel NAD+-linked opine dehydrogenase from a soil isolate Arthrobacter sp. strain 1C belongs to an enzyme superfamily whose members exhibit quite diverse substrate specificites. Crystals of this opine dehydrogenase, obtained in the presence or absence of co-factor and substrates, have been shown to diffract to beyond 1.8 ? resolution. X-ray precession photographs have established that the crystals belong to space group P21212, with cell parameters a = 104.9, b = 80.0, c = 45.5 ? and a single subunit in the asymmetric unit. The elucidation of the three-dimensional structure of this enzyme will provide a structural framework for this novel class of dehydrogenases to enable a comparison to be made with other enzyme families and also as the basis for mutagenesis experiments directed towards the production of natural and synthetic opine-type compounds containing two chiral centres.     

A theory for the anisotropic and inhomogeneous dielectric properties of proteins

Using results from the dielectric theory of polar solids and liquids, we calculate the mesoscopic, spatially-varying dielectric constant at points in and around a protein by combining a generalization Kirkwood-Fr?hlich theory along with short all-atom molecular dynamics simulations of equilibrium protein fluctuations. The resulting dielectric permittivity tensor is found to exhibit significant heterogeneity and anisotropy in the protein interior. Around the surface of the protein it may exceed the dielectric constant of bulk water, especially near the mobile side chains of polar residues, such as K, N, Q, and E. The anisotropic character of the protein dielectric selectively modulates the attractions and repulsions between charged groups in close proximity.     

beta-sheet hydrogen bonding patterns in cystine peptides

Cystine peptides have been shown to adopt conformations in organic solvents that mimic small beta-sheets. Relative hydrogen bond strengths, beta-strand aggregation, and the identity of individual hydrogen bond donors and acceptors have been identified through hydrogen/deuterium exchange.     

HNF4α Antagonists Discovered by a High-Throughput Screen for Modulators of the Human Insulin Promoter

Hepatocyte nuclear factor (HNF)4α is a central regulator of gene expression in cell types that play a critical role in metabolic homeostasis, including hepatocytes, enterocytes, and pancreatic β cells. Although fatty acids were found to occupy the HNF4α ligand-binding pocket and were proposed to act as ligands, there is controversy about both the nature of HNF4α ligands as well as the physiological role of the binding.?Here, we report the discovery of potent synthetic HNF4α antagonists through a high-throughput screen for effectors of the human insulin promoter. These molecules bound to HNF4α with high affinity and modulated the expression of known HNF4α target genes. Notably, they were found to be selectively cytotoxic to cancer cell lines in?vitro and in?vivo, although in?vivo potency was limited by suboptimal pharmacokinetic properties. The discovery of bioactive modulators for HNF4α raises the possibility that diseases involving HNF4α, such as diabetes and cancer, might be amenable to pharmacologic intervention by modulation of HNF4α activity.     

轿车车门断面设计的原则和方法

介绍了轿车车门断面设计的基本方法,探讨了控制断面的作用和设置原则．结合车门间隙、车门密封、车门运动校核及车门结构件连接等具体设计过程,分析了车门断面设计中需要考虑的控制要素,阐述了轿车车门断面设计的基本思路和程序．     

A smoothness criterion for monotonicity-preserving subdivision

In this paper we study subdivision schemes that both interpolate and preserve the monotonicity of the input data, and we derive a simple ratio condition that guarantees the continuous differentiability of the limit function. We then show that the condition holds for both a scheme of Kuijt and van Damme, based on rational functions, and a scheme of Sabin and Dodgson, based on square roots.