Long-standing enzyme structure mystery solved

Posted by ap507 at Jul 10, 2014 07:15 PM |
Sometimes one proton can make all the difference...
Long-standing enzyme structure mystery solved

The core of the Munich reactor FRM II used, showing the blue Cherenkov radiation. Copyright: A. Heddergott / TUM

An international team of researchers, led by the University of Leicester, has solved a long-standing mystery in biology, by identifying the molecular structure of a vital biological chemical.

An important enzyme called a heme (or haem, as in haemoglobin) contains an iron atom which becomes oxidised when the enzyme is in a particular state. The question that has taxed biological chemists for decades is whether this oxidation involves just an oxygen atom (O), or a hydroxyl group (OH). The difference being one hydrogen ion, or in other words, a proton.

Over the years, some scientists arguing that the heme carries a proton, while others have been equally adamant that no proton is present. But this is no saga of Lilliputian pedantry over which end to crack open a boiled egg.  Resolving this fundamental inconsistency has implications for understanding of oxidative processes within living cells, which is crucially important for drug development.

Structures of proteins are commonly determined using X-ray crystallography but this is unsuitable for identifying hydrogen atoms so Professor Peter Moody from our Department of Biochemistry and Professor Emma Raven from our Department of Chemistry - working with colleagues in France, Germany and Manchester - have now solved the mystery using a different method: neutron crystallography.

And the answer turns out to be… the heme is NOT protonated. But, unexpectedly, the results showed that one of the amino acid side chains on the molecule IS doubly protonated, which raises questions of its own.

The paper ‘Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase’ has now been published in Science.

The research was supported by The Leverhulme Trust, BBSRC, The Wellcome Trust, Bruker UK Ltd, EU FP7, Institut Laue-Langevin and Heinz Maier-Leibnitz Zentrum.