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Protein α-helices often terminate in recognizable helix-capping motifs. The origin of thermodynamic stability for one such motif is now well understood.
Bacteria are covered in sugars that facilitate the establishment of pathogenic or symbiotic relationships with other cells. Microarrays of carbohydrate-binding proteins now can provide quick snapshots of these sugar coats as they change during the bacterial life cycle and differ among bacterial strains.
Looked at from the outside of the cell, proteins are often hidden behind a forest of sugar chains. Using a sugar analog to introduce thiols onto the tips of the branches of this forest alters cell attachment and has unexpected consequences for cell differentiation.
Enzymes that catalyze the formation of (S)-allantoin from the product of the urate oxidase reaction have been identified. This finding answers the longstanding question of how living organisms produce a single enantiomer of allantoin.
The report of a new class of potent and highly selective inhibitors of Bcr-abl highlights the potential for a truly leukemia-specific drug with no expected off-target activity. GNF-2, as a representative compound of this class, may have inspired the identification of a region of Bcr-abl that is amenable to drug design, just as imatinib did almost a decade ago.
Studies have linked the Fucα(1-2)Gal modification of neuronal glycoproteins to cognitive processes such as learning and memory. The identification of synapsins Ia and Ib as the main Fucα(1-2)Gal-bearing neuronal proteins not only suggests previously unknown molecular mechanisms of neuronal plasticity but also indicates the existence of previously unknown glycosylation pathways in neurons.
DNA in the nucleus of mammalian cells is extensively associated with proteins. Potential anticancer agents can access, recognize and alkylate nucleosomal DNA, even at sites that seem completely occluded by association with histone proteins.
Modern single-molecule tools, when applied to enzymes, challenge fundamental concepts of catalysis by uncovering mechanistic pathways, intermediates and heterogeneities hidden in the ensemble average. It is thus reassuring that the Michaelis-Menten formalism, a pillar of enzymology, is upheld, if reinterpreted, even when visualizing single turnover events with a microscope focus.
A small-molecule inhibitor of protein secretion has been found that targets Cdc42, a regulator of the secretory pathway. This compound acts through a previously undescribed mechanism—by recruiting a protein inhibitor.
Ion channels have essential roles in the nervous system. An engineered ligand-gated channel with a photoactivated switch will be useful for addressing several issues in neuronal signaling.
Neurotransmitter binding to a member of the Cys-loop receptor superfamily elicits opening of an ion channel by inducing a change in the configuration of a prolyl imide bond. Engineering a series of mutant receptors to contain proline analogues with a range of cis/trans preferences demonstrates the molecular basis for channel gating.
Methylation is a key regulatory event in several biological processes. The enzymatic transfer by methyltransferases of extended carbon chain analogs of S-adenosylmethionine to DNA opens up new avenues for investigating biological methylation.
Hedgehog signaling has important and pleiotropic roles in embryonic and adult tissues. A small-molecule agonist of this pathway has been shown to act by targeting the transmembrane protein Smoothened.
The zebrafish has become a popular model organism to investigate many biological processes, in part owing to the combination of facile genetic manipulation and rapid, external embryonic development. The application of large-scale screening to identify chemical suppressors of a cancer-prone mutant highlights new technology for whole organism–based small-molecule discovery.
Development of small-molecule agonists against members of the tumor necrosis factor (TNF) receptor superfamily remains a considerable challenge. Presentation of ligand-derived peptides on a trimeric scaffold may point the way toward development of potent small-molecule agonists against this biologically important protein superfamily.
Sir2 is a key regulator in promoting longevity in response to a low-calorie diet. A new role for nitric oxide in promoting mitochondrial synthesis may be the reason why.
