Volume 6 Issue 11, November 2010

The capability to generate multi-omic data sets raises the issue of resource allocation for data generation versus data curation and integration. The initial experience of researchers shows that the effort required for the latter can be much greater than that for the former.

Ten significantly active new (R)-transaminases, still very rare enzymes, were found among 21 designed variants obtained from nothing more than existing transaminase structures and alignment of pertinent fingerprints of annotated sequences.

ATP synthase synthesizes and hydrolyzes ATP by a unique rotational mechanism. A new study elucidates an important step of the catalytic mechanism, the timing of the release of the reaction product P_i in ATP hydrolysis.

Aminoacylation of tRNA is the cellular process for providing aminoacyl donors for the ribosome synthesis of polypeptides. New research highlights an unexpected structural overlap between enzymes involved in this process and those involved in the biosynthesis of cyclodipeptides, an important class of bioactive molecules.

Some cyclodipeptides are unusual in that their cyclic scaffold is created from activated, amino-acid–loaded tRNA substrates. Structural and biochemical evidence now demonstrates that the enzymes that perform this reaction are homologous to tRNA synthetases and use a covalently bound intermediate.

Purine catabolism is typically thought to yield metabolic waste material. However, bioinformatics analysis, coupled with structural and biochemical investigations, now demonstrates that the central carbons of the purine ring can be recycled into glycine in B. subtilis and other bacteria.

The identification or development of enzymes with new functions remains a significant challenge. A new strategy uses rationally selected sequences anticipated to serve as functional motifs to search the wealth of available genomic data, successfully yielding 17 (R)-selective amine transaminases.

A magnetic tweezer system that arrests the rotary ATP synthase F1 at the ATP-hydrolysis step provides an order of events to the chemomechanical cycle involving ADP release before phosphate release upon F1 rotation in ATP-hydrolysis mode.

Structural analysis of protein kinase A had previously focused on static pictures with bound inhibitors. The first analyses of the protein with a substrate peptide identify dynamic hot spots and slow steps in catalysis, pointing toward a model of conformational selection in binding.

A Xenopus laevis two-reporter screen identifies the antihelminthic drug pyrvinium as an inhibitor of the Wnt/β-catenin signaling pathway that works by activating CK1α, which is likely working at the level of Pygopus, a core transcriptional component of the Wnt pathway.

The ability of constrained mutants of the estrogen receptor ligand-binding domain to dictate different conformations of bound partial agonists indicates that the ability of compounds to stabilize each state determines the degree of agonist activity.