Spotting the invisible

High resolution x-ray structure of the enzyme adenylate kinase trapped in a transient structural state by a covalent disulfide bond. Credit: Umea University

Chemists at Umeå University have succeeded in mapping structures along with functions of a transient enzyme state. By modifying the enzyme adenylate kinase, researchers were able to isolate the molecule along with study the idea using the quantitative techniques X-ray crystallography along with nuclear magnetic resonance (NMR) spectroscopy. The results have been published from the journal PNAS.


“We have today come one step closer to a general understanding of how enzymes function. in which is usually vital for future designs of novel enzymes in biotechnological applications,” says Magnus Wolf-Watz, associate professor at the Department of Chemistry at Umeå University.

Biological life is usually dependent on a large number of cellular, chemical reactions in which are often extremely slow along with can take months or years to complete. For chemical along with biological time-scales to match, chemical reactions are sped up in cells with the use of enzymes as efficient biocatalysts.

Over the last decade of research the idea has been made clear in which enzyme structures in which only exist briefly along with transiently can be entirely essential for the catalytic function. So far, the idea has not been possible to study these states in detail due to the simple fact in which they are invisible to traditional spectroscopic techniques. today, researchers at the Department of Chemistry at Umeå University in Sweden have managed to capture a transient state central to the function from the essential enzyme adenylate kinase. The short-term state was possible to enrich by exchanging two amino acids from the enzyme with the reactive amino acid cysteine.

“the idea’s initially in which anyone has managed to study a transient enzyme state directly using spectroscopic along with quantitative techniques. With the use of our methods, we were able to in detail describe both the structure along with the function of the enzyme from the specific transient phase,” says Magnus Wolf-Watz, who led the study together with postdoc Michael Kovermann, who is usually today holding a group leadership at the University of Konstanz in Germany.

The results indicated in which the function in one enzyme is usually entirely dependent on its inherent dynamics, along with without dynamics the enzyme could be rendered useless. Furthermore, the idea turned out in which the transient state bound its substrate molecules much stronger than the natural proteins. The results gave us further clues as to how enzymes can speed up reactions with such incredible specificity along with efficacy. All the while, the method in which we developed can be generally useful in studies of additional enzymes.”

Magnus Wolf Watz’s NMR team has collaborated with the x-ray crystallographers Uwe H. Sauer along with Elisabeth Sauer-Eriksson on the study.

“We have had a long-term along with very productive collaboration. in which is usually a not bad example of how important the collaborative atmosphere found at Umeå University is usually, along with how we should cherish along with further develop the idea in future,” says Magnus Wolf-Watz.


Explore further:
‘Invisible’ protein structure explains the power of enzymes

More information:
Michael Kovermann et al. Structural basis for ligand binding to an enzyme by a conformational selection pathway, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1700919114

Journal reference:
Proceedings of the National Academy of Sciences

Provided by:
Umea University

Spotting the invisible

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