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 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)


ACS Chem Biol 2006 Sep 19
PMID:Symbiosis: Chemical biology at Wisconsin. 1716 30


ACS Chem Biol 2006 Sep 19
PMID:The evolution and refinement of a chemical biology training program: A Canadian perspective. 1716 31


ACS Chem Biol 2006 Sep 19
PMID:Graduate education chemical biology at the University of Michigan. 1716 32


ACS Chem Biol 2006 Sep 19
PMID:Designing a curriculum that goes beyond a list of topics. 1716 33


ACS Chem Biol 2006 Sep 19
PMID:The education system for chemical biology in Japanese universities. 1716 34

Trimethylation of histone H3 Lys4 (H3K4) is associated with transcriptional activation. One of the chief effectors of H3K4 methylation is mixed-lineage leukemia 1 (MLL1), a gene that is disrupted by chromosomal translocation in acute leukemia and a master regulator of Hox and other genes. In a recent paper, core components of the human MLL histone methyltransferase (MT) complex were found to form a structural platform, with one component (WDR5) mediating association between the specific histone H3K4 substrate and the MT. This novel regulatory mechanism, which is conserved from yeast to human, is required for both methylation and downstream target gene transcription.
ACS Chem Biol 2006 Sep 19
PMID:MLL core components give the green light to histone methylation. 1716 35

Glycosyltransferases (GTs) are ubiquitous enzymes that catalyze the transfer of a sugar moiety from an activated donor to an acceptor and thus play important roles in natural product biogenesis, virulence, and biomolecular recognition. Sugars are often critical for bioactivity of natural products, and methodologies for creating diverse glycoforms of these compounds are highly desirable. A recent study demonstrates that several GTs involved in natural product biosynthesis catalyze reversible reactions. Sugar exchange and aglycon exchange strategies were used to exploit this reversibility to generate >70 calicheamicin analogues.
ACS Chem Biol 2006 Sep 19
PMID:Glyco-stripping and glyco-swapping. 1716 36

Modular polyketide synthases (PKSs) are large multifunctional proteins that synthesize complex polyketide metabolites in microbial cells. A series of recent studies confirm the close protein structural relationship between catalytic domains in the type I mammalian fatty acid synthase (FAS) and the basic synthase unit of the modular PKS. They also establish a remarkable similarity in the overall organization of the type I FAS and the PKS module. This information provides important new conclusions about catalytic domain architecture, function, and molecular recognition that are essential for future efforts to engineer useful polyketide metabolites with valuable biological activities.
ACS Chem Biol 2006 Sep 19
PMID:Clearing the skies over modular polyketide synthases. 1716 37

Because of analytical limitations, multiple animals or plants are typically required to identify natural products. Using a unique 1-mm high-temperature superconducting NMR probe, we directly examined the chemical composition of defensive secretions from walking stick insects. Individual milkings were dissolved in D2O without purification and examined by NMR within 10 min of secretion. We found that Anisomorpha buprestoides secretes similar quantities of glucose and mixtures of monoterpene dialdehydes that are stereoisomers of dolichodial. Different individual animals produce different stereoisomeric mixtures, the ratio of which varies between individual animals raised in the same container and fed the same food. Another walking stick, Peruphasma schultei, also secretes glucose and a single, unique stereoisomer that we are naming "peruphasmal". These observations suggest a previously unrecognized significance of aqueous components in walking stick defensive sprays. Single-insect variability of venom demonstrates the potential importance of chemical biodiversity at the level of individual animals.
ACS Chem Biol 2006 Sep 19
PMID:Single insect NMR: A new tool to probe chemical biodiversity. 1716 38

Broadly applicable strategies facilitating direct and selective modulation of the intracellular levels of physiologically important small molecules are essential for dissecting their integral and multiple roles in cellular processes. Therefore, we have been exploring the suitability of RNA aptamers for this purpose. Using the Escherichia coli heme biosynthetic pathway as a simple model of a negative feedback regulated process, we show that heme-binding RNA aptamers, developed in vitro and expressed intracellularly, induce a heme-dependent growth defect in an E. coli heme auxotroph defective in converting delta-aminolevulinic (delta-ALA) acid into downstream products. Relative to a control oligonucleotide, the aptamers also induce delta-ALA accumulation in cells grown under heme-limiting conditions. Increasing the concentration of heme in the media completely reverses both the growth defect and delta-ALA accumulation, except for two aptamers for which reversal is partial. Thus, these aptamers specifically target their cognate ligand in vivo and functionally modulate its intracellular concentration, demonstrating that RNA aptamers are useful tools for elucidating the role of heme and possibly other small molecules in regulating cellular networks.
ACS Chem Biol 2006 Sep 19
PMID:Utilizing RNA aptamers to probe a physiologically important heme-regulated cellular network. 1716 39


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