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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

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

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>