Science News
from research organizations

Mysteries of enzyme mechanism revealed

Date:
November 29, 2016
Source:
University of Leicester
Summary:
A breakthrough advance has been made 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.
Share:
FULL STORY

Neutron diffraction from Compound II of Ascorbate peroxidase.
Credit: Institut Laue-Langevin/ University of Leicester

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 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."

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.


Story Source:

Materials provided by University of Leicester. Note: Content may be edited for style and length.


Journal Reference:

  1. Hanna Kwon, Jaswir Basran, Cecilia M. Casadei, Alistair J. Fielding, Tobias E. Schrader, Andreas Ostermann, Juliette M. Devos, Pierre Aller, Matthew P. Blakeley, Peter C. E. Moody, Emma L. Raven. Direct visualization of a Fe(IV)–OH intermediate in a heme enzyme. Nature Communications, 2016; 7: 13445 DOI: 10.1038/ncomms13445

Cite This Page:

University of Leicester. "Mysteries of enzyme mechanism revealed." ScienceDaily. ScienceDaily, 29 November 2016. <www.sciencedaily.com/releases/2016/11/161129084225.htm>.
University of Leicester. (2016, November 29). Mysteries of enzyme mechanism revealed. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/11/161129084225.htm
University of Leicester. "Mysteries of enzyme mechanism revealed." ScienceDaily. www.sciencedaily.com/releases/2016/11/161129084225.htm (accessed May 23, 2017).

RELATED STORIES