Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Screens save protein-profile time

17.09.2001

Two new techniques will assist the rapid cataloguing of proteins’ roles in the cell.


Looks don’t matter: new techniques find enzymes like this one by function not form

Decoding the human genome sequence was merely a preliminary step towards understanding how living cells work. Two new techniques should assist the next step: working out the functions of all the proteins that the genes encode1,2.

Selectively sticking to small molecules is central to most proteins’ function. Proteins generally have delicately sculpted binding sites, clefts into which certain target molecules, called substrates, fit like a key in a lock. Often this binding allows the protein to act as a catalyst, chemically transforming the substrate.

The functional role of a particular protein is therefore revealed, or at least hinted at, by what it binds. Two teams have now identified the substrates of a range of proteins.

Current methods for assigning a function to a protein rely on a detailed knowledge of its structure or shape. Proteins are long chains of interlinked amino acids, folded up into a compact shape. If two proteins have very similar amino-acid sequences, they probably share similar functions.

Deducing the sequences of each of the many thousands of proteins in a cell is a slow business. Another approach is to use X-ray crystallography to determine the protein’s three-dimensional shape - where each atom sits.

Researchers are now trying to develop automated systems for the rapid crystallographic study of many proteins3. Unfortunately, some proteins share a similar function even if they look different, as long as their binding sites fit similar substrates.

So Gerhard Klebe and colleagues at the University of Marburg in Germany have compared the binding sites of various proteins and evaluated the similarity of their substrates - regardless of any differences either in sequence or overall protein shape. In other words, the method spots commonalities hidden from existing techniques.

The researchers compared the binding sites of two enzymes, one from yeast and one from Escherichia coli bacteria. Because the enzymes share the same function even though only 20% of their amino-acid sequences overlap, a sequence comparison would not recognize that they do the same job. But the computer program identified the E. coli enzyme as the closest match to the yeast enzyme from 5,445 other protein binding sites.

Spotting relationships such as this could also aid drug design by suggesting new small molecules that might block the activity of certain enzymes.

Meanwhile, Peter Schultz and co-workers at the Scripps Research Institute in La Jolla, California, have developed a way to screen huge numbers of proteins simultaneously and pick out those that bind to particular target molecules.

The researchers have taken the complex protein mixture that every cell contains and presented it with small substrates tagged with strands of PNA, a molecule similar to DNA and capable of binding to it. The PNA acts as a kind of label: its chemical structure is like a bar code for the attached substrate.

When a protein latches onto the substrate, the PNA latches onto a strand of DNA at a particular location on a grid-like array. The PNA-DNA pairing glows, lighting up a grid point on the array and signalling the presence of the substrate-binding protein.

References

  1. Schmitt, S., Hendlich, M. & Klebe, G. From structure to function: a new approach to detect functional similarity among proteins independent from sequence and fold homology. Angewandte Chemie, 40, 3141 - 3144, (2001).
  2. Winssinger, N., Harris, J. L., Backes, B. J. & Schultz, P. G. From split-pool libraries to spatially addressable microarrays and its application to functional proteomic profiling. Angewandte Chemie, 40, 3152 - 3155, (2001).
  3. Abola, E., Kuhn, P., Earnest, T. & Stevens, R. C. Automation of X-ray crystallography. Nature Structural Biology, 7, 973 - 977, (2001).

PHILIP BALL | Nature News Service

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>