Biosciences News

University of Washington (UW) researchers have designed a novel protein with properties that could lead to the generation of new photoactive proteins. This three-fold symmetric, self-assembling protein homotrimer contains a highly stable noncanonical amino acid. Noncanonical amino acids are not found among the 20 encoded amino acids in the body and can contain modifications to allow for new functionality. In this case, this amino acid contains a bipyridine group that chelates metal, thereby introducing new photochemical properties into the protein interface, and nucleating the formation of the homotrimer.

An article published last month in PNAS describes this work from a team of scientists led by David Baker at UW, which included Jose Henrique Pereira, Banumathi Sankaran, and Peter Zwart of the Molecular Biophysics & Integrated Bioimaging Division (MBIB). The MBIB scientists developed the crystal screen that was used to crystallize the novel protein and performed X-ray crystallography on Beamline 8.2.1 in the Berkeley Center for Structural Biology at the Advanced Light Source. Their X-ray crystallographic analysis of the homotrimer showed that the design process had near-atomic-level accuracy, demonstrating that computational protein design together with the utilization of noncanonical amino acids could be used to generate novel protein functions. These methods could be used to develop new therapeutics, biomaterials, and metalloproteins with useful optical or photochemical properties.

Calcium channel blockers are widely prescribed for heart and blood-vessel diseases. With the help of the high-intensity x-ray beams and remotely controlled robots at the Advanced Light Source (ALS), two groups of scientists from University of Washington have revealed, at atomic resolution, how two different classes of calcium channel blocker drugs produce their therapeutic effects. The researchers took advantage of the remotely controllable robot automounter available in the Berkeley Center for Structural Biology at the ALS to screen a large number of crystals for the best diffraction. The tunable x-ray source also allowed them to collect anomalous diffraction data at Beamlines 8.2.1 and 8.2.2 with bromine-incorporated drugs, which was critical for locating the drug molecules in the crystal. The results pave the way for optimizing these classic compounds for safer and more reliable pharmaceutical applications. Read the ALS Science Highlight.

In collaboration with DOE Joint Genome Institute (JGI) researchers, the team led by David Baker of the University of Washington reports that structural models have been generated for 12 percent of the protein families that previously had no structural information available. Read more at JGI News.

The Biosciences Area launched its Twitter account one year ago. @LBNLBioSci has served as a tool to disseminate the Area’s achievements in energy, environment and health, and has so far attracted 409 followers. To celebrate the one year anniversary, the Biosciences communications team has released a listicle on seven of the Area’s bacterial, fungal and microbial discoveries. Read the listicle here and follow @LBNLBioSci.

In Nature, a team led by University of East Anglia scientists conducted a comparative genomic analysis involving three diatoms by tapping expertise from the DOE Joint Genome Institute (JGI), who conducted all sequencing and annotation. Read more at JGI News.