Volume 12 Issue 8, August 2016

Hsp90 is an energy-consuming molecular chaperone that activates oncogenic proteins in a complicated multi-step reaction. Photoinduced electron transfer (PET) quenching experiments with a fluorescent reporter have now identified molecular transitions at multiple timescales in the chaperone cycle of Hsp90.

Glucose metabolism has long been thought to operate with exquisite specificity and near-optimal efficiency. New findings show, however, that two glycolytic enzymes produce minor products that inhibit other enzymes involved in central carbon metabolism unless they are further metabolized by a novel enzyme.

A pH-activatable fluorescent sensor targeted to bone tissue allows intravital imaging of osteoclast pH changes with greater photo-stability in mice, revealing insights into osteoclast motility and proton extrusion.

Biochemical analysis, and imaging using a copper-sensitive fluorescent sensor, demonstrate that copper regulates cAMP-mediated lipolysis by inhibiting the activity of the cAMP-degrading phosphodiesterase PDE3B.

A small-molecule compound binds to the RGS domain of axin, promotes the degradation of β-catenin and Ras through the GSK3β-mediated destruction complex, and reduces the growth of KRAS and APC mutant colorectal cancer cell lines.

The glycolytic enzymes GAPDH and pyruvate kinase produce 4-phosphoerythronate and 2-phospho-L-lactate, which block metabolic flux. A newly identified conserved metabolic repair enzyme, phosphoglycolate phosphatase, eliminates these side products.

A newly synthesized nitroxide-based probe containing a fluorophore with high quantum yield at relatively long wavelengths can detect endogenously derived lipid-derived radicals and has therapeutic potential in a model of hepatocellular carcinoma.

Biochemical and enzymological analysis reveals that SIRT6 G60A mutant shows very little deacetylase activity but is able to perform defatty acylation, which is required for the regulation of protein secretion.

Characterization of three DUF89 subfamilies representing all domains of life reveals that members function as metal-dependent phosphatases that help eliminate a wide range of damaged phosphometabolites.

Monitoring conformational switching within the chaperone Hsp90 using high-resolution fluorescent probes based on photoinduced electron transfer defines a cooperativity mechanism as well as a two-step restructuring of the ATP lid segment.

WelO5 is an iron- and 2-oxoglutarate-dependent halogenase involved in welwitindolinone biosynthesis. A collection of X-ray crystal structures reveals the active-site geometry and ligand dynamics required for small-molecule halogenation by WelO5.

Monolyso-cardiolipin (MLCL) accumulates in individuals with Barth syndrome, but this can be mitigated by stabilization of cardiolipin from metabolism to MLCL via assembly into supercomplexes of oxidative phosphorylation proteins. This process was found to be defective in subjects with Barth syndrome.

MS analysis of yeast transfer RNA precursors (pre-tRNAs) isolated at different stages of tRNA processing and maturation reveals the presence of 5′-terminal methylguanosine cap structures that protect pre-tRNA from 5′-exonucleolytic degradation.