Search results for "Timer"
showing 10 items of 119 documents
DNA origami as a nanoscale template for protein assembly
2009
We describe two general approaches to the utilization of DNA origami structures for the assembly of materials. In one approach, DNA origami is used as a prefabricated template for subsequent assembly of materials. In the other, materials are assembled simultaneously with the DNA origami, i.e. the DNA origami technique is used to drive the assembly of materials. Fabrication of complex protein structures is demonstrated by these two approaches. The latter approach has the potential to be extended to the assembly of multiple materials with single attachment chemistry.
Covalently linked multimers of gold nanoclusters Au102(p-MBA)44and Au∼250(p-MBA)n
2016
We present the synthesis, separation, and characterization of covalently-bound multimers of para-mercaptobenzoic acid (p-MBA) protected gold nanoclusters. The multimers were synthesized by performing a ligand-exchange reaction of a pre-characterized Au102(p-MBA)44 nanocluster with biphenyl-4,4′-dithiol (BPDT). The reaction products were separated using gel electrophoresis yielding several distinct bands. The bands were analyzed by transmission electron microscopy (TEM) revealing monomer, dimer, and trimer fractions of the nanocluster. TEM analysis of dimers in combination with molecular dynamics simulations suggest that the nanoclusters are covalently bound via a disulfide bridge between BP…
Fluidizing the Membrane by a Local Anesthetic: Phenylethanol Affects Membrane Protein Oligomerization
2010
The exact mechanism of action of anesthetics is still an open question. While some observations suggest specific anesthetic-protein interactions, nonspecific perturbation of the lipid bilayer has also been suggested. Perturbations of bilayer properties could subsequently affect the structure and function of membrane proteins. Addition of the local anesthetic phenylethanol (PEtOH) to model membranes and intact Escherichia coli cells not only affected membrane fluidity but also severely altered the defined helix-helix interaction within the membrane. This experimental observation suggests that certain anesthetics modulate membrane physical properties and thereby indirectly affect transmembran…
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
2014
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
A Structural Model of the Human α7 Nicotinic Receptor in an Open Conformation
2015
International audience; Nicotinic acetylcholine receptors (nAchRs) are ligand-gated ion channels that regulate chemical transmission at the neuromuscular junction. Structural information is available at low resolution from open and closed forms of an eukaryotic receptor, and at high resolution from other members of the same structural family, two prokaryotic orthologs and an eukary- otic GluCl channel. Structures of human channels however are still lacking. Homology modeling and Molecular Dynamics simulations are valuable tools to predict structures of unknown proteins, however, for the case of human nAchRs, they have been unsuccessful in providing a stable open structure so far. This is du…
Structure and Function of CutC Choline Lyase from Human Microbiota Bacterium Klebsiella pneumoniae.
2015
CutC choline trimethylamine-lyase is an anaerobic bacterial glycyl radical enzyme (GRE) that cleaves choline to produce trimethylamine (TMA) and acetaldehyde. In humans, TMA is produced exclusively by the intestinal microbiota, and its metabolite, trimethylamine oxide, has been associated with a higher risk of cardiovascular diseases. Therefore, information about the three-dimensional structures of TMA-producing enzymes is important for microbiota-targeted drug discovery. We have cloned, expressed, and purified the CutC GRE and the activating enzyme CutD from Klebsiella pneumoniae, a representative of the human microbiota. We have determined the first crystal structures of both the choline-…
Structural characterization of the Borrelia burgdorferi outer surface protein BBA73 implicates dimerization as a functional mechanism.
2013
Borrelia burgdorferi, which is the causative agent of Lyme disease, is transmitted from infected Ixodes ticks to a mammalian host following a tick bite. Upon changing the host organism from an Ixodes tick to a warm-blooded mammal, the spirochete must adapt to very different conditions, which is achieved by altering the expression of several genes in response to a changing environment. Recently, considerable attention has been devoted to several outer surface proteins, including BBA73, that undergo dramatic upregulation during the transmission of B. burgdorferi from infected Ixodes ticks to mammals and that are thought to be important for the establishment and maintenance of the infection. T…
10-A cryoEM structure and molecular model of the Myriapod (Scutigera) 6x6mer hemocyanin:understanding a giant oxygen transport protein
2009
Oxygen transport in Myriapoda is maintained by a unique 6x6mer hemocyanin, that is, 36 subunits arranged as six hexamers (1x6mers). In the sluggish diplopod Spirostreptus, the 1x6mers seem to operate as almost or fully independent allosteric units (h approximately 1.3; P(50) approximately 5 torr), whereas in the swift centipede Scutigera, they intensively cooperate allosterically (h approximately 10; P(50) approximately 50 torr). Here, we show the chemomechanical basis of this differential behavior as deduced from hybrid 6x6mer structures, obtained by single-particle cryo-electron microscopy of the Scutigera 6x6mer (10.0 A resolution according to the 0.5 criterion) and docking of homology-m…
Strombine dehydrogenase in the demosponge Suberites domuncula: Characterization and kinetic properties of the enzyme crucial for anaerobic metabolism
2008
Previously, the cDNA and the respective gene for a presumed tauropine dehydrogenase (TaDH) from Suberites domuncula (GenBank accession nos. AM712888, AM712889) had been annotated. The conclusion that the sequences encode a TaDH had been inferred from the 68% identity with the TaDH protein from the marine demosponge Halichondria japonica. However, subsequent enzymatic assays shown here indicate that the presumed S. domuncula opine dehydrogenase is in fact a strombine dehydrogenase (StDH). The enzyme StDH is highly specific for glycine and is inhibited by an excess of the substrate pyruvate. Besides kinetic data, we report in this study also on the predicted tertiary and quaternary structure …
Evolution of Snake Venom Disintegrins by Positive Darwinian Selection
2008
PII-disintegrins, cysteine-rich polypeptides broadly distributed in the venoms of geographically diverse species of vipers and rattlesnakes, antagonize the adhesive functions of beta(1) and beta(3) integrin receptors. PII-disintegrins evolved in Viperidae by neofunctionalization of disintegrin-like domains of duplicated PIII-snake venom hemorrhagic metalloproteinase (SVMP) genes recruited into the venom proteome before the radiation of the advanced snakes. Minimization of the gene (loss of introns and coding regions) and the protein structures (successive loss of disulfide bonds) underpins the postduplication divergence of disintegrins. However, little is known about the underlying genetic …