Showing papers in "Chemistry & Biology in 2007"

TL;DR: It is revealed that approximately 85% of brain 2-AG hydrolase activity can be ascribed to MAGL, and that the remaining 15% is mostly catalyzed by two uncharacterized enzymes, ABHD6 and ABHD12.

TL;DR: Data support the hypothesis that multivalent enhancement of K(D), not an enhanced rate of endocytosis, is the key factor resulting in the improved biological targeting by these drug delivery platforms.

TL;DR: Glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function.

TL;DR: Biophysical analysis revealed that 2-alkyl-3-hydroxy-4-quinolones form complexes with iron(III) at physiological pH, and a secondary function for PQS in iron entrapment to facilitate siderophore-mediated iron delivery is revealed.

TL;DR: It is shown that WFA binds to the intermediate filament (IF) protein, vimentin, by covalently modifying its cysteine residue, which is present in the highly conserved alpha-helical coiled coil 2B domain.

TL;DR: A "genomisotopic approach," which employs a combination of genomic sequence analysis and isotope-guided fractionation to identify unknown compounds synthesized from orphan gene clusters containing nonribosomal peptide synthetases, resulted in the discovery of orfamide A, founder of a group of bioactive cyclic lipopeptides.

TL;DR: The structure of KR from the first module of the tylosin PKS was determined and reveals how polyketides are guided into the active site by key residues in different KR types.

TL;DR: Four mechanistic models, not mutually exclusive, that could account for the specific reactions of molecular oxygen with a fatty acid in the LOX or COX active site are presented.

TL;DR: Comparison of this activator bound and the previously published apoenzyme complex supports a model in which GlcN6P does not induce a conformational change in the RNA, as is typical of other riboswitches, but instead functions as a catalytic cofactor for the reaction.

TL;DR: Fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.

TL;DR: An immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus is reported, providing a strong foundation for further investigations of Immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

TL;DR: It is shown that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells, and these studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.

TL;DR: In this article, the authors developed a system for producing "unnatural" flavonoids and stilbenes in Escherichia coli, which included a substrate synthesis step for CoA esters synthesis from carboxylic acids by 4-coumarate:CoA ligase, a polyketide synthesis stage for conversion of the co-a esters into flavanones, and a modification step for modification of the flavanone by flavone synthase, flavone 3beta-hydroxylase and flavonol synthase.

TL;DR: It is demonstrated that RNA quadruplexes readily form in vivo, and tuneable mRNA-based devices that enable modulation of gene expression by a predictable but thus far unknown mechanism are introduced.

TL;DR: This work synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells, and consequently inhibit the multiplication of HIV.

TL;DR: A carbohydrate microarray-based approach for the rapid, facile analysis of glycosaminoglycan-protein interactions was reported, and it was shown that fibroblast growth factor family members have distinct sulfation preferences.

TL;DR: An automated high-throughput screening method is presented that identifies synthetic riboswitches that display extremely low background levels of gene expression in the absence of the desired ligand and robust increases in expression in its presence.

TL;DR: Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic.

TL;DR: Analysis of the substrate-binding site of the KS domain suggests that a loop region at the homodimer interface influences KS substrate specificity, and a model for the interaction of the catalytic domains with the acyl carrier protein (ACP) domain is described.

TL;DR: It is demonstrated that P-glycoprotein19 (PGP19) is a target for Gravacin and participates in its inhibition of gravitropism and E1174 as an important residue for PGP19 activity and its ability to form active transport complexes with PIN1.

TL;DR: Direct correlation between potency of the compounds as CYP51 inhibitors and their antiparasitic effect in TB and TC cells implies essential requirements for endogenous sterol production in both trypanosomes and suggests a lead structure with a defined region most promising for further modifications.

TL;DR: The ribosomal polymerization of alpha-hydroxy acids by means of genetic code reprogramming is reported, indicating that high-fidelity ribosome expression of polyesters was possible and opens a door for the mRNA-directed synthesis of backbone-altered biopolymers.

TL;DR: Evidence from NMR studies is provided that a significant proportion of the oxime-linked core monosaccharide is in the ring-closed form, and this form selectively interacts with a carbohydrate-binding protein.

TL;DR: It is demonstrated that McjB and McjC, encoded by genes in the MccJ25 gene cluster, catalyze the maturation of MCCJ25, and it is shown that putative lasso peptides are widespread among Proteobacteria and Actinobacteria.

TL;DR: Inhibitors with low micromolar affinity which effectively block binding of Runx1 to CBFbeta are developed and treated of the human leukemia cell line ME-1 with these compounds shows decreased proliferation, indicating these are good candidates for further development.

TL;DR: It is proposed and discussed a working model suggesting that deregulation of the thioredoxin reductase/thiOREDoxin redox system is a major mechanism involved in the anticancer activity of the investigated gold(III)-dithiocarbamato complexes.

TL;DR: A suite of structures described provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket, and information gained will inform the design and optimization of more effective small-molecule inhibitors of BoNT or A-LC.

TL;DR: The discovery of the endocannabinoid system, and its targeting with two new pharmaceutical preparations now on the market in several countries, represent the most recent example of how studies on medicinal plants and on the mechanism of their biological effects can reveal, through a chain of breakthroughs, new systems of endogenous signals and physiological phenomena that can become the source of novel strategies for unmet therapeutic challenges.

TL;DR: The results identify the metabolic rearrangements that maintain the CoASH pool which is critical to mitochondrial functions, including gluconeogenesis, fatty acid oxidation, and the tricarboxylic acid and urea cycles.

TL;DR: Development of molecular probes that selectively inhibit the major catalytic subunit, LMP2, of the immunoproteasome are reported, and it is shown that these compounds irreversibly modify the L MP2 subunit with high specificity.