Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Searching for purpose in proteins

01.11.2010
A small-molecule screening method helps scientists probe mysteries of protein function

As scientists continue to acquire immense amounts of genomic and biochemical data from various organisms, they routinely find themselves confronted by proteins of known structure but enigmatic function—and resolving those mysteries may require a chemical-based ‘fishing expedition’.

“The discovery of small molecules that bind to and disrupt the function of a specific target is an important step in chemical biology, especially for poorly characterized proteins,” explains Isao Miyazaki, a researcher with Hiroyuki Osada’s team at the RIKEN Advanced Science Institute in Wako. “We call these small molecules ‘bioprobes’.”

Recent work from Miyazaki and Osada demonstrates a highly effective strategy for identifying such bioprobes, which they have used to identify inhibitors of the human pirin protein1. Pirin is conserved across a diverse array of organisms, and has been tentatively linked to cancer malignancy in humans; however, little is known about how this protein might govern tumor progression.

The investigators produced glass slides containing a large array of small molecules, which they then treated with cellular extracts containing pirin protein fused to DsRed, a fluorescent tag. By identifying the spots selectively highlighted by the labeled protein, they were able to zoom in on a candidate molecule with apparently high specificity and binding affinity for pirin, which they named triphenyl compound A (TPh A).

High-resolution structural analysis demonstrated that TPh A inserts itself deeply within the pirin protein, and Miyazaki sees this as proof of the utility of their screening strategy. “There has been a question of whether ligands identified using chemical array approaches typically bind at shallow surfaces,” he says. “Our study confirms that chemical array methods can identify molecules that bind to buried pockets in proteins.”

Accordingly, TPh A appears to act as an effective functional inhibitor. Melanoma cells treated with this compound showed a marked reduction in cell migration, and this effect appears to arise from TPh A-mediated disruption of the interaction between pirin and the cancer-related protein Bcl3. By analyzing cellular gene expression profiles, the researchers subsequently uncovered evidence that pirin and Bcl3 collaborate to switch on the SNAI2 gene, which is known to contribute to tumor progression and metastatic growth.

These findings demonstrate the potential of bioprobe screening as a strategy for uncovering hidden protein functions. Miyazaki and Osada anticipate that TPh A will provide a valuable tool for future investigations of the role of pirin in other cancers and may even prove useful for studying related proteins from other organisms.

The corresponding author for this highlight is based at the Antibiotics Laboratory, RIKEN Advanced Science Institute

Journal information

1. Miyazaki, I., Simizu, S., Okumura, H., Takagi, S. & Osada, H. A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. Nature Chemical Biology 6, 667–673 (2010).

gro-pr | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/eng/research/6435
http://www.researchsea.com

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>