Effect of Extensin - Like Cotton Proteins on Eukaryotic Cell Gene

The effect of extensin-like cotton proteins (ELP) on animal cell gene (KML cell culture) was studied. Cells perish (50%) at protein dose 100 g/mL (cytotoxic effect). DNA fragmentation is not observed. Cell death from ELP is hypothesized to occur via necrosis resulting from destruction of intracellular biochemical processes     

Isolation and General Properties of Cotton Extensin-Like Proteins

Extensin-like proteins (ELP) from 2-day sprouts and suspended cotton culture were isolated and characterized.__________Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 63–65, January–February, 2005.     

Hydroxyproline-Containing Plant Proteins

Data on hydroxyproline-containing proteins of plant cell walls were reviewed. Structure-function relationships were discussed.     

Proteins of Bare - and Downy-Seeded Cotton Varieties

An investigation of the composition of fiber-forming proteins and enzymes established a correlation between the degree of seed downiness in genetic cotton varieties and enzyme activity.     

Comparative Analysis of Proteins from Cytoplasmatic Organelles of Pollen from Certain Cotton Species

The protein composition of cytoplasmatic organelles within species, phylogenetic group, and genus was investigated using electrophoretic separation of protein fractions.     

Variations in Proteins Dielectric Constants

Using a new semi-empirical method for calculating molecular polarizabilities and the Clausius−Mossotti relation, we calculated the static dielectric constants of dry proteins for all structures in the protein data bank (PDB). The mean dielectric constant of more than 150,000 proteins is with a standard deviation of 0.04, which agrees well with previous measurement for dry proteins. The small standard deviation results from the strong correlation between the molecular polarizability and the volume of the proteins. We note that non-amino acid cofactors such as Chlorophyll may alter the dielectric environment significantly. Furthermore, our model shows anisotropies of the dielectric constant within the same molecule according to the constituents amino acids and cofactors. Finally, by changing the amino acid protonation states, we show that a change of pH does not have a significant effect on the dielectric constants of proteins.     

Specific Transport of Target Molecules by Motor Proteins in Microfluidic Channels

Direct transport powered by motor proteins can alleviate the challenges presented by miniaturization of microfluidic systems. There have been several recent attempts to build motor‐protein‐driven transport systems based on simple capturing or transport mechanisms. However, to achieve a multifunctional device for practical applications, a more complex sorting/transport system should be realized. Herein, the proof of concept of a sorting device employing selective capture of distinct target molecules and transport of the sorted molecules to different predefined directions is presented. By combining the bottom‐up functionality of biological systems with the top‐down handling capabilities of micro‐electromechanical systems technology, highly selective molecular recognition and motor‐protein‐based transport is integrated in a microfluidic channel network.     

Molecular Modeling of the Three‐Dimensional Structure of Human Sphingomyelin Synthase

Sphingomyelin synthase (SMS) produces sphingomyelin and diacylglycerol from ceramide and phosphatidylcholine. It plays an important role in cell survival and apoptosis, inflammation, and lipid homeostasis, and therefore has been noticed in recent years as a novel potential drug target. In this study, we combined homology modeling, molecular docking, molecular dynamics simulation, and normal mode analysis to derive a three‐dimensional structure of human sphingomyelin synthase (hSMS1) in complex with sphingomyelin. Our model provides a reasonable explanation on the catalytic mechanism of hSMS1. It can also explain the high selectivity of hSMS1 towards phosphocholine and sphingomyelin as well as some other known experimental results about hSMS1. Moreover, we also derived a complex model of D609, the only known small‐molecule inhibitor of hSMS1 so far. Our hSMS1 model may serve as a reasonable structural basis for the discovery of more effective small‐molecule inhibitors of hSMS1.     

Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment

The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) innate immunity system is a membrane receptor of paramount importance as therapeutic target. Its assembly, upon binding of Gram-negative bacteria lipopolysaccharide (LPS), and also dependent on the membrane composition, finally triggers the immune response cascade. We have combined ab-initio calculations, molecular docking, all-atom molecular dynamics simulations, and thermodynamics calculations to provide the most realistic and complete 3D models of the active full TLR4 complex embedded into a realistic membrane to date. Our studies give functional and structural insights into the transmembrane domain behavior in different membrane environments, the ectodomain bouncing movement, and the dimerization patterns of the intracellular Toll/Interleukin-1 receptor domain. Our work provides TLR4 models as reasonable 3D structures for the (TLR4/MD-2/LPS)₂ architecture accounting for the active (agonist) state of the TLR4, and pointing to a signal transduction mechanism across cell membrane. These observations unveil relevant molecular aspects involved in the TLR4 innate immune pathways and will promote the discovery of new TLR4 modulators.     

蓖麻毒素A链(RTA)功能域突变体构效关系的量子化学研究

结合对蓖麻毒素A链(RTA)功能域氨基酸(Tyr80,Trr123,Gln177,Arg180)点突变后对其生物活性影响的实验研究,利用半经验量子化学AMI方法对RTA功能域及其点突变进行了理论计算.通过分析前线分子轨道性质和能级,从理论上探讨了其功能域点突变对其生物活性的影响,并预测了突变体(Tyr123→TrP)比RTA生物活性高.     

Evaluation of 3- and 4-Phenoxybenzamides as Selective Inhibitors of the Mono-ADP-Ribosyltransferase PARP10

Intracellular ADP-ribosyltransferases catalyze mono- and poly-ADP-ribosylation and affect a broad range of biological processes. The mono-ADP-ribosyltransferase PARP10 is involved in signaling and DNA repair. Previous studies identified OUL35 as a selective, cell permeable inhibitor of PARP10. We have further explored the chemical space of OUL35 by synthesizing and investigating structurally related analogs. Key synthetic steps were metal-catalyzed cross-couplings and functional group modifications. We identified 4-(4-cyanophenoxy)benzamide and 3-(4-carbamoylphenoxy)benzamide as PARP10 inhibitors with distinct selectivities. Both compounds were cell permeable and interfered with PARP10 toxicity. Moreover, both revealed some inhibition of PARP2 but not PARP1, unlike clinically used PARP inhibitors, which typically inhibit both enzymes. Using crystallography and molecular modeling the binding of the compounds to different ADP-ribosyltransferases was explored regarding selectivity. Together, these studies define additional compounds that interfere with PARP10 function and thus expand our repertoire of inhibitors to further optimize selectivity and potency.     

Study of the interaction of aglycon of daunorubicin with human serum albumin by spectroscopy and modeling

The interaction between aglycon of daunorubicin (DNR-A) and human serum albumin (HSA) was investigated using fluorescence quenching and modeling. Results shown that fluorescence quenching of HSA by DNR-A resulted from the formation of DNR-A-HSA complex. The quenching constants were determined via measurement of the binding affinity between DNR-A and HSA using the Stern-Volmer equation. The thermodynamic parameters DeltaG, DeltaH, DeltaS and the binding distance r were calculated. Furthermore, SFS and UV spectra suggested that the complex changed the conformation of HSA and that hydrophobic interactions played a major role in DNR-A-HSA association, which was in good agreement with the results of the modeling study. Moreover, the SFS technique was successfully applied to determine the total proteins in biology samples with satisfactory results.     

Biopolymers for biocatalysis: Structure and catalytic mechanism of hydroxynitrile lyases

Hydroxynitrile lyases catalyze the reversible cleavage of α-cyanohydrins to yield hydrocyanic acid and the corresponding aldehyde or ketone. Besides its biological interest, this class of enzymes is also of relevance in industrial biocatalysis for the enantioselective condensation of HCN with a variety of aldehydes and ketones. Several distinctly different types of hydroxynitrile lyases (HNLs) are known, which must have originated through convergent evolution from different ancestral proteins. Three-dimensional structural data are known for three classes of hydroxynitrile lyases. Insights into the reaction mechanisms emerged from a combination of structural, enzyme kinetic, spectroscopic, and molecular modeling data. For all three types of HNLs, mechanisms involving acid–base catalysis were proposed. In members belonging to the α,β-hydrolase type, the amino acid residues of the catalytic triad presumably act as general acid/base, whereas for flavine adenine dinucleotide (FAD)-dependent HNLs a single histidine residue fulfills this function. In the third type of HNL—which is related to carboxypeptidase—acid–base catalysis involves the carboxylate of the C-terminal residue. The catalytic relevance of a positive electrostatic potential in the active site was suggested in some of the mechanistic proposals. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 479–486, 2004     

Scaling law for the radius of gyration of proteins and its dependence on hydrophobicity

The scaling law between the radius of gyration and the length of a polymer chain has long been an interesting topic since the Flory theory. In this article, we seek to derive a unified formula for the scaling exponent of proteins under different solvent conditions. The formula is obtained by considering the balance between the excluded volume effect and elastic interactions among monomers. Our results show that the scaling exponent is closely related to the fractal dimension of a protein's structure at the equilibrium state. Applying this formula to natural proteins yields a 2/5 law with fractal dimension 2 at the native state, which is in good agreement with other studies based on Protein Data Bank analysis. We also study the dependence of the scaling exponent on the hydrophobicity of a protein chain through a simple two‐letters HP model. The results provides a way to estimate the globular structure of a protein, and could be helpful for the investigation of the mechanisms of protein folding. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 207–214, 2009     

Chemoselective Capture of Glycans for Analysis on Gold Nanoparticles: Carbohydrate Oxime Tautomers Provide Functional Recognition by Proteins

Open or closed : N‐Glycosyl oxyamine versus open‐chain glycosyl oxime is the key to protein recognition on glyconanoparticles. Unprotected glycans are captured by oxime formation with a novel bifunctional reagent and the resulting glycan‐linker conjugates are anchored to gold nanoparticles (AuNPs). These glyconanoparticles maintain the structural integrity of glycans in the study of protein–carbohydrate interactions (see figure).