Volume 11 Issue 2, February 2015

Terminal triple bonds feature in natural products, but their biosynthesis is little known. Now a terminal acetylenase has been characterized for substrate specificity for the first time, and an application to 'bio-click' chemistry has been shown by incorporation of the moiety into natural product scaffolds.

Lysophosphatidylserines (lyso-PSs) are an emerging class of signaling lipids implicated in human inflammatory and autoimmune diseases. A newly discovered phosphatidylserine-specific lipase, ABHD16A, together with the recently described lyso-PS lipase ABHD12 shed light on the in vivo regulation of lyso-PS, providing a potential enzymatic target for modulating neuroinflammatory responses.

The reliable identification of microRNA (miRNA) targets remains an elusive goal. A new technique, using specially modified synthetic miRNAs to directly capture bound RNAs, brings us closer.

Recent studies on two enzyme classes operating at the membrane interface showcase an unanticipated degree of structural plasticity involving domain swapping and marked secondary structure reshuffling. This structural variability in topology is key to functional diversification and catalytic prowess.

Characterization of four enzymes involved in biosynthesis of the plant metabolite and anticancer agent noscapine completes this pathway and identifies an unusual acetyl protecting group strategy that defines the order of enzymatic steps.

Validation of the cellular targets of microRNAs remains an ongoing priority. miR-CLIP, a new method based on psoralen crosslinking, immunoprecipitation and biotin affinity pulldowns, was applied to determine the miR-106a targetome, which included the H19 lncRNA.

Genetic evidence suggested jamABC from the jamaicamide biosynthetic pathway were responsible for the synthesis of the terminal alkyne functional group. Biochemical studies now confirm this activity and demonstrate the insertion of alkynes into two unrelated natural products.

Biocatalysis can take advantage of an enzyme's inherent reactivity regardless of its physiological role, as shown for a terpene cyclase turned Brønsted acid catalyst after its active site pocket was mutated while the activated aspartic acid was retained.

A family of cyclic lipopeptide natural products named lysocins was isolated from a soil bacteria sample and was found to exhibit antimicrobial actions. Genetic and biochemical evidence showed that lysocin E targets bacterial menaquinone.

Disulfide trapping and FRET studies define an agonist-induced conformational change in mGlu2 from inactive symmetric dimers with an interface at transmembrane domains (TMs) 4 and 5 to an active state with TM6s serving as the dimer interface.

Desmosterol acts as an endogenous RORγ agonist during differentiation of CD4⁺ T cells into the T_H17 lineage, where there is increased cholesterol biosynthesis and uptake and decreased cholesterol metabolism and efflux that cause accumulation of desmosterol.

Although nonspecific chaperones such as GroEL can increase evolvability by helping slightly destabilized mutants, a dedicated assembly chaperone decreases evolvability of the CO₂ fixation enzyme Rubisco, providing insights into Rubisco's poor catalytic power.

The metabolic enzyme GAPDH exhibits oxidative inactivation in response to H₂O₂. A proton relay system was identified that enhances H₂O₂ sensitivity of GAPDH distinct from its catalytic activity, which ensures viability under oxidative stress.

ABHD16A is identified as a major enzyme catalyzing production of lyso-PS from phosphatidylserine (PS). A new ABHD16A inhibitor and knockout mice show a dynamic interplay occurring during inflammation between ABHD16A and disease-linked ABHD12, an enzyme that degrades lyso-PS.