Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Observed "live": water is an active team player for enzymes

19.09.2011
In biologically active enzyme substrate compounds, as can be found in medicines, water plays a more decisive role than has been imagined up to now.

The surrounding water acts like an "adhesive", in order to keep the substrate at the right place on an enzyme. For this, the dynamism of the water is retarded. Scientists at the RUB under Prof. Dr. Martina Havenith (Physical Chemistry) in close cooperation with the group of Prof. Irit Sagi from the Israeli Weizmann Institute have been able to observe and prove the retardation of the water's dynamism "live" for the first time in close.

The researchers are reporting on their results in "Nature Structural & Molecular Biology“. Observed "live": water is an active team player for enzymes
RUB researchers report in Nature Structural & Molecular Biology
Water acts as an "adhesive" in biological enzyme substrate compounds
In biologically active enzyme substrate compounds, as can be found in medicines, water plays a more decisive role than has been imagined up to now. The surrounding water acts like an "adhesive", in order to keep the substrate at the right place on an enzyme. For this, the dynamism of the water is retarded. Scientists at the RUB under Prof. Dr. Martina Havenith (Physical Chemistry) in close cooperation with the group of Prof. Irit Sagi from the Israeli Weizmann Institute have been able to observe and prove the retardation of the water's dynamism "live" for the first time in close. The researchers are reporting on their results in "Nature Structural & Molecular Biology“.

Which role does the solvent play?

Enzymes are natural substances accelerating and controlling the metabolic processes in the body. They are, for example, of central importance for the immune system, as they control the balance between activating and inhibiting defensive reactions and play an important role in inflammation reactions. It had been known for some time that enzymatic functions take place in various solvents at highly differing speeds. But up to now, the contribution made by the solvent - this is water in biological processes - on a molecular level had not yet been clarified.

Two new techniques combined

Prof. Havenith’s group at the RUB and Prof. Irit Sagi’s group at the Institute of Structural Biology of the Weizmann Institute have combined two newly developed experimental techniques, in order directly to prove the significance of the water for the enzymatic functions. The object of their study was matrix metalloproteases (MMP). MMPs can be found outside our cells in the so-called extracellular matrix, where they fulfil central tasks as message transmitters, managers or maintenance units on a molecular level. As a result of the decomposition of the extracellular matrix, the MMP are actively and directly involved in the reconstruction of our tissue, e.g. in embryo or tumour growth and in wound healing. The numerous possible fields of use make this family of enzymes an important field of study for the development of medicines. "The mechanism for the enzymatic activity of the matrix metalloproteases is however not yet known on a molecular level, which poses still challenges on any synthetic drug design," says Prof. Havenith.

Precise characterisation of all "players"

For precise understanding of the reaction, the researchers looked at all the "players" involved: the matrix metalloprotease enzyme as the “lock”, its activating substrate - the "key" - and the water as a solvent, the reaction environment. In the experiment, the scientists investigated the binding of the substrate to the MMP. With the help of time-resolved X-ray spectroscopy, they were able to characterise precisely the structural changes in the vicinity of the active enzyme centre (here: of the zinc atom) with atomic resolution. With the help of kinetic THz absorption spectroscopy (KITA), they recorded the changes in time of the fast water movements.

The role of water for future drug design

In various MMP-protein combinations, an unambiguous correlation was found between the fluctuations of the water network, the structure changes and the function. Molecular dynamic simulations provided an explanation for the observations: While the substrate has not found yet the "correct point" of the enzyme - the lock-, the water dynamism, i.e. the opening and reformation of hydrogen bonds between water molecules (the "terahertz dance" of the water), is fast. At the same time as the substrate is docking onto the active centre, the water movement in the environment slows down. Water then acts then more like a kind of adhesive there, which keeps the substrate at this point. This change of the THz dance of the water with the formation of the enzyme-substrate binding is however exclusively observed in biologically active enzyme-substrate combinations. "The retardation of the water dynamism, observed for the first time, thus appears to be an essential part of the functional control", says Prof. Havenith. "Therefore, in future, taking the role of the water into account in the development of medicines, for example for tumour therapy, might become important."

"Solvation Science@RUB“

This work is part of "Solvation Science@RUB“, the research topic of the new center of molecular spectroscopy and simulation of solvent controlled processes at the RUB (ZEMOS), and of the excellence cluster application of the RUB “RESOLV”, which is now under review at the German council of science. In chemistry, process engineering and biology, there are an enormous number of publications describing solvents as inert (passive) media for molecular processes. Beyond this traditional view, the active role of the solvent is however becoming more and more visible. New experimental and theoretical methods now permit investigation, description and systematic control of the structure, dynamism and kinetics of complex solvation phenomena on a molecular level. "So it is now most timely to develop general models with a predictive power for solvation processes", says Prof. Havenith. Precisely that is the objective of "Solvation Science@RUB".

Title

M. Grossman, B. Born, M. Heyden, D. Tworowski, G. Fields, I. Sagi, M. Havenith: Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site. Nature Structural & Molecular Biology, Advance Online Publication (AOP), doi: 10.1038/nsmb.2120

http://www.nature.com/nsmb/journal/vaop/ncurrent/abs/nsmb.2120.html

Further information

Prof. Dr. Martina Havenith, Faculty of Chemistry and Biochemistry of the Ruhr-Universität Bochum, Chair of Physical Chemistry II, Tel. 0234/32-24249, martina.havenith@rub.de

Editorial: Jens Wylkop

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de/
http://www.nature.com/nsmb/journal/vaop/ncurrent/abs/nsmb.2120.html

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke 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: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>