Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The hidden lives of proteins

03.12.2009
For the first time, experimental evidence shows that hidden protein structures are essential for catalysis

An important Brandeis study appearing in the December 3 issue of Nature raises the curtain on the hidden lives of proteins at the atomic level. The study reports that for the first time, researchers used x-ray crystallography and nuclear magnetic resonance (NMR) techniques to directly visualize protein structures essential for catalysis at the rare high-energy state. The study also showed how the motions of these rare, or hidden, structures collectively, directly contribute to enzyme catalysis.

In doing so, the study also suggests new molecular sites for potential drug targets, the cornerstone of rational drug design. Drugs may bind, or dock, to the infrequent high-energy states of target enzymes that have been hidden to traditional structural methods. The thinking is that drugs can be designed by docking algorithms to a collection of protein structures, not just one, providing better bio-molecular targeting.

This study comes in the wake of earlier Brandeis studies aimed at advancing understanding of protein function using pioneering techniques such as NMR. For a long time, scientists viewed proteins more or less as macromolecular wallflowers, venturing out onto the atomic-level dance floor to perform only during catalysis, their active state.

Then, several years ago, Brandeis biophysicist Dorothee Kern reported in Nature that her lab's experiments using NMR also linked protein function to their much rarer high-energy state, in the absence of catalysis. That study helped put to rest the conventional wisdom that proteins actually rest at all.

This Nature study takes Kern's research to the next level, seeing the high-resolution structure of the hidden, high-energy state for the first time. For this success, high –resolution x-ray crystallography was further pushed by analyzing electron density data previously discarded as "noise" and by collecting data at ambient temperature. The protein of interest is human cyclophilin A, an enzyme that is highjacked by the HIV virus to aid its own replication.

But it was thanks to some clever protein design together with dynamic NMR spectroscopy that provided direct experimental evidence that the hidden structures in the high-energy state are in fact essential for catalysis. The researchers revealed what happens when proteins flip from the rare state to a major state in a process called interconversion. If this flip is fast, then the enzyme does its job fast, but if the flip is slow, as in the designer enzyme, then the enzyme operates slowly.

"People always focused on the chemistry—accelerating the reaction through catalyzing the chemical step of the substrates. What we've shown is that protein dynamics is as important as the chemical step," said Kern, a Howard Hughes Medical Institute Investigator. "Basically, all the steps need to be choreographed just right, like steps for a beautiful dancer. An enzyme can only function well with the perfect choreography of all the components."

Said Kern: "We now can show directly that the higher energy states are always there and that these hidden, rare states are absolutely essential for protein function."

Laura Gardner | EurekAlert!
Further information:
http://www.brandeis.edu

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk 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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>