Nav: Home

Mysteries of enzyme mechanism revealed

November 29, 2016

An international research team led by the University of Leicester has made a breakthrough advance by trapping an intermediate in the mechanism of enzymes called heme peroxidases and determining its structure using a beam of neutrons from the heart of a nuclear reactor.

The advance is announced today (29 November) in an online publication in Nature Communications. The Leicester team members say they are delighted by their finding which could change the way we understand how these enzymes work through 'wonderful collaborations' with scientists at European facilities such as the Institut Laue-Langevin (ILL) in Grenoble and FRM-II in Munich, as well as the Diamond Light Source in Oxfordshire and the EPR centre at Manchester University. Professors Emma Raven and Peter Moody from the University of Leicester's Institute of Structural and Chemical Biology led the team that developed a new method to trap and analyse the enzyme's reaction steps.

Professor Moody of the Department of Molecular and Cell Biology, said: "Using beams of neutrons instead of X-rays lets us see the position of hydrogen atoms without altering the chemical state. These enzymes go through two intermediate steps, a couple of years ago we used neutron cryo-crystallography to show the hydrogens in the first step (published in Science), and since then a great deal of work by our team has allowed us find a way to trap the next step. It had been believed that this second step did not hold hydrogen at the reactive centre, however this work clearly shows the hydrogen and so we have to re-think the way the enzyme works."

Heme enzymes have an iron atom in a special chemical group called a porphyrin, this is the same as in hemoglobin, the molecule that carries oxygen in our blood, but in heme peroxidase enzymes it is used to pull apart peroxide for many different biochemical processes, these include getting rid of damaging compounds in the cell and the making of new molecules that the cell needs.

Professor Raven from the University's Department of Chemistry said: "The exact nature of these enzyme intermediates has been the subject of a long-standing controversy and conflicting interpretation of indirect evidence. At least we have been able to see these directly, this really is the 'holy grail' of heme enzyme research."
-end-
  • The work has been funded by a BBSRC project grant to Professors Moody and Raven, an equipment grant from Wellcome Trust and beamtime awarded by the ILL for LADI-III and by FRM-II for BioDIFF.

  • This work was mainly conducted by Dr Hanna Kwon (University of Leicester) with the support of the other authors, the neutron data were collected and processed with Dr Matthew Blakeley at the LADI-III beamline at ILL.

The online publication will be on the Nature Communications website on the 29th of November. The DOI for this article is: DOI: 10.1038/ncomms13445

NOTE TO NEWSDESK:

For interviews contact:

Professor Emma Raven: emma.raven@le.ac.uk

Professor Peter Moody: peter.moody@le.ac.uk

Dr Matthew Blakeley: blakeleym@ill.fr

About the Leicester Institute of Structural and Chemical Biology

The Leicester Institute of Structural and Chemical Biology was created in 2016 with the aim of bringing together established strengths in structural biology, chemical biology and single-molecule research. The new Institute will take advantages of synergies in research technologies and approaches to deliver major advances in both fundamental and translational research.

The Institute's research is organised into four inter-related research strands:

Understanding the structure and mechanism of macromolecular complexes

Some of the most challenging questions in biology involve understanding the structures and mechanism of action of the molecular machines that carry out the processes of life.

Structure-based drug discovery and design

Structural biology provides us enormous insight into the mechanism of action of macromolecules and complexes. At the same time it provides detailed insights into strategies to develop small and medium-sized molecules that can alter protein functions and serve as effective therapeutics.

Using single molecule techniques to understand complex and dynamic biological processes

Many fundamental cellular processes rely on highly dynamic interactions between macromolecules and macromolecular complexes. Single molecule techniques allow us to observe and understand these processes in real time.

Chemical probes and compound libraries development

Understanding how macromolecules carry out their many diverse activities requires an understanding of the underlying chemistry which determines the behaviour of these complexes. By exploiting this chemistry we are able to manipulate macromolecular function and activity. This is important both for drug development, but also the development of research tools.

About Institut Laue-Langevin - the Institut Laue-Langevin (ILL) is an international research centre based in Grenoble, France. It has led the world in neutron-scattering science and technology for almost 40 years, since experiments began in 1972. ILL operates one of the most intense neutron sources in the world, feeding beams of neutrons to a suite of 40 high-performance instruments that are constantly upgraded. Each year 1,200 researchers from over 40 countries visit ILL to conduct research into condensed matter physics, (green) chemistry, biology, nuclear physics, and materials science. The UK, along with France and Germany is an associate and major funder of the ILL.

University of Leicester

Related Hydrogen Articles:

Superconductivity: It's hydrogen's fault
Last summer, it was discovered that there are promising superconductors in a special class of materials, the so-called nickelates.
Hydrogen energy at the root of life
A team of international researchers in Germany, France and Japan is making progress on answering the question of the origin of life.
Hydrogen alarm for remote hydrogen leak detection
Tomsk Polytechnic University jointly with the University of Chemistry and Technology of Prague proposed new sensors based on widely available optical fiber to ensure accurate detection of hydrogen molecules in the air.
Preparing for the hydrogen economy
In a world first, University of Sydney researchers have found evidence of how hydrogen causes embrittlement of steels.
Hydrogen boride nanosheets: A promising material for hydrogen carrier
Researchers at Tokyo Institute of Technology, University of Tsukuba, and colleagues in Japan report a promising hydrogen carrier in the form of hydrogen boride nanosheets.
World's fastest hydrogen sensor could pave the way for clean hydrogen energy
Hydrogen is a clean and renewable energy carrier that can power vehicles, with water as the only emission.
Chemical hydrogen storage system
Hydrogen is a highly attractive, but also highly explosive energy carrier, which requires safe, lightweight and cheap storage as well as transportation systems.
Observing hydrogen's effects in metal
Microscopy technique could help researchers design safer reactor vessels or hydrogen storage tanks.
The 'Batman' in hydrogen fuel cells
In a study published in Nature on Jan. 31, researchers at the University of Science and Technology of China (USTC) report advances in the development of hydrogen fuel cells that could increase its application in vehicles, especially in extreme temperatures like cold winters.
Paving the way for more efficient hydrogen cars
Hydrogen-powered vehicles emit only water vapor from their tailpipes, offering a cleaner alternative to fossil-fuel-based transportation.
More Hydrogen News and Hydrogen Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Processing The Pandemic
Between the pandemic and America's reckoning with racism and police brutality, many of us are anxious, angry, and depressed. This hour, TED Fellow and writer Laurel Braitman helps us process it all.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Invisible Allies
As scientists have been scrambling to find new and better ways to treat covid-19, they've come across some unexpected allies. Invisible and primordial, these protectors have been with us all along. And they just might help us to better weather this viral storm. To kick things off, we travel through time from a homeless shelter to a military hospital, pondering the pandemic-fighting power of the sun. And then, we dive deep into the periodic table to look at how a simple element might actually be a microbe's biggest foe. This episode was reported by Simon Adler and Molly Webster, and produced by Annie McEwen and Pat Walters. Support Radiolab today at Radiolab.org/donate.