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The neurosteroid pregnenolone (P5) is known to be required for zebrafish embryonic cell movement and microtubule stability. By binding the microtubule plus-end tracking protein CLIP-170 (depicted as a bulldozer) and opening it from its folded state to promote binding to microtubules, p150Glued and LIS1, P5 enhances polymerization of tubulin (bricks) into microtubules to facilitate cell migration and the development of the organism (buildings). Cover art by Erin Dewalt, based on artwork from Wei-Yao Ku. Article, p636.
Genetic code expansion for synthesis of proteins containing noncanonical amino acids is a rapidly growing field in synthetic biology. Creating optimal orthogonal translation systems will require re-engineering central components of the protein synthesis machinery on the basis of a solid mechanistic biochemical understanding of the synthetic process.
Biological sulfonate incorporation is mediated by 3′-phosphoadenosine-5′-phosphosulfate–dependent sulfotransferases and, to a lesser extent, arylsulfate sulfotransferases. An unusual two-enzyme strategy for sulfonate mobilization involving both types of sulfotransferases has been revealed during antibiotic biosynthesis, which uses a new polyketide as the sulfonate shuttle.
In vivo, hydrogenases require maturases for active site incorporation. However, in vitro, an active site model with limited catalytic activity could be incorporated into the apo form of [FeFe]-hydrogenase without the aid of maturases, generating enzyme with native activity.
Cryo-EM, crystallography, biochemical experiments and computational approaches have been used to study different intermediate states of the Aeromonas hydrophila toxin aerolysin en route to pore formation. These results reveal that an unexpected and marked rotation of the core aerolysin machinery is required to unleash the membrane-spanning regions.
In cells, di-iron hydrogenases require three maturases to facilitate proper assembly of metal clusters. Reconstitution experiments with synthetic cofactor mimics coupled with functional and spectroscopic characterization now show these helper proteins are not needed in vitro to form highly active H2-producing catalysts.
Two families of sulfotransferases are known, but the natural sulfate source for the PAPS-independent enzymes was not clear. Investigation of the caprazamycin pathway reveals a type III PKS generates a chemical reagent that is sulfated by a PAPS-dependent sulfotransferase to generate the unknown sulfate donor.
Inteins catalyze protein splicing, excising themselves from the final polypeptide sequence. Biochemical and structural analysis of multiple inteins now demonstrates that these constructs can swap domains before splicing, leading to unexpected hybrid products.
Near-atomistic models of the prepore and membrane-inserted pore conformations derived from a combination of crystallography, cryo-EM, single-particle analysis, molecular simulation and modeling reveal a swirling mechanism of membrane insertion and pore formation by aerolysin.
Opsinamides are nonretinoid inhibitors that compete with 9-cis-retinal for binding to melanopsin Opn4 without affecting rod- and cone-mediated visual responses but affecting tolerance to light and light exacerbation of migraine.
EZH2 and EED are components of the Polycomb repressive complex 2 (PRC2), a ‘writer’ complex involved in histone methylation. A stapled peptide that disrupts the EZH2-EED interaction arrests growth in PRC2-dependent leukemia cells and offers an alternative mode for EZH2 inhibition.
The metallothionein-like, 23-amino-acid peptide NO-inducible nitrosothionein does not protect against heavy metal toxicity like its homologues, but instead helps relieve nitrosative stress by reaction of six cysteine residues to form SNO adducts, which are recycled back to thiols by thioredoxin.