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Modular polyketide synthases are intensively studied as exquisite synthetic machines generating bioactive natural products. The enoylreductase, a common component of these machines, has been structurally and functionally characterized, revealing a new complex architecture.
Crk-like (CrkL) is a key signaling protein that mediates the leukemogenic activity of Bcr-Abl. Structural investigations show that the intramolecular assembly of CrkL is entirely distinct from that of CrkII, shedding light on how CrkL specifically mediates Bcr-Abl signaling.
Heterocycles such as thiazoles are introduced into ribosomally synthesized peptide metabolites by post-translational modification. The enzyme that installs those rings has been identified, providing insight into heterocyclization biochemistry and the potential capabilities of an entire protein family.
Lymphoid tyrosine phosphatase (LYP) is often mutated in humans suffering from autoimmune diseases. A recent study proposes a mechanism by which LYP can cause these diseases and suggests that drugs against LYP could be a useful treatment.
RNA molecules have diverse functional roles, including silencing genes, catalyzing biochemical reactions and sensing chemicals that control gene expression. Biologists have drawn from nature's toolbox to construct engineered RNA molecules with versatile capabilities and can now begin to automate the design of libraries of regulatory RNAs.
Sensing of the plant hormone auxin involves formation of a co-receptor complex consisting of an F-box protein and an AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressor. Distinct co-receptor combinations might provide cells with an unexpectedly broad range of auxin-sensing capacities and contribute to diverse transcriptional programs activated by different auxin levels in various developmental contexts.
The activity of the anaphase-promoting complex is regulated by the autoubiquitination of Cdc20. How this autoubiquitination is regulated remains an open question. The pharmacological inhibitor TAME now provides insight into this regulation.
Owing to population aging, the number of individuals suffering from Alzheimer's disease is rapidly increasing; consequently, finding an effective treatment is becoming an increasingly important goal. The use of O-GlcNAcase inhibitors is emerging as a promising track to prevent and slow disease progression.
The cell wall of tubercle bacilli is targeted by many drugs. A new adamantyl urea compound unveils MmpL3, a member of the resistance, nodulation and division protein family, as the long-sought trehalose monomycolate transporter, essential for translocation of mycolic acids into the cell envelope.
Selective reduction of keto groups contributes to the structural diversity of polyketide natural products. New research on fungal polyketide synthases reveals unusual biosynthetic programming in which a single ketoreductase domain shows different stereochemical preferences on the basis of substrate-chain length.
Osmolytes that normally accumulate in cells to equilibrate osmotic stress are also called chemical chaperones because of their ability to stabilize native proteins in vitro. A recent paper shows that various chemical chaperones differently alter the cellular milieu and permit the appearance of osmolyte-specific protein mutant variants during evolution.
A combination of genetic and pharmacological approaches using mouse leukemia models show that STAT5 phosphorylation is one of the major drivers of the proliferation of Philadelphia chromosome–positive (BCR-ABL-positive or Ph+) chronic myeloid leukemia. Once BCR-ABL expression has been established, JAK2 is required only for lymphoid cell transformation, not for the maintenance of the lymphoid or myeloid leukemia.
Metal ions are frequently used in enzyme catalysis. The extension of computational methods to metalloenzyme redesign opens up new ways to construct enzymes with new functions.
20(S)-hydroxycholesterol, a naturally occurring oxysterol, activates the Hedgehog signaling pathway by directly binding an allosteric site on Smoothened.
Patch-clamp fluorometry measurements of cAMP binding and channel opening combined with global kinetic fitting revealed that ligand binding to the tetrameric hyperpolarization-activated cyclic nucleotide–gated channel is favored at the second and fourth binding events.
Mucopolysaccharidoses are inherited disorders in which inactivation of lysosomal enzymes results in accumulation of glycosaminoglycans within cells, causing tissue and organ dysfunction. A method to determine the unique end structures of the accumulated glycosaminoglycans offers a new way for diagnosis.
