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Substantial investment in Leiden centre for NMR spectroscopy

Paramagnetism. An obscure occult practice? No. It’s one of the newest scientific methods for mapping the behaviour of proteins with great precision. Marcellus Ubbink has been awarded 3 million euro by NWO and Leiden University to purchase a very powerful instrument. The goal: to acquire greater insight into health and illness.

How does NMR spectroscopy work?

Comparison of NMR images of the same sample of cytochrome P450 (a protein) at 600 and 800 MHz. The 800 MHz gives clearer signals and contains more information.

Nuclear Magnetic Resonance (NMR) is an important technique for studying proteins at atomic level. In this technique, an organic substance, in this case a protein, is brought into a magnetic field and irradiated with radio waves. Atom nuclei then emit a signal. Ubbink: ‘Since every signal has a slightly different frequency, which can be observed separately, it is as if the protein is covered in ‘antennae’. Each antenna provides information about its own environment around the protein.’ Proteins are complex structures which consist of elastic, dynamic components. The instrument measures these movements over a certain period of time and the researchers then convert these data into images.


What is paramagnetic NMR?


A: Proteins. B: Dynamics of short-term protein complexes. C: Protein complex (grey in crystal form and red in liquid form)

By adding an unpaired electron, for instance in the form of a metal atom, to a protein, a strong interaction occurs between the electron and the other atomic nuclei, as a result of which signals can be measured even better. This effect can be used to study how proteins bind with each other, thereby enabling all kinds of processes in the living cell. Ubbink studies the dynamics of protein complexes and has already shown that they attract one other, rotate around one other and briefly connect with one another before releasing one another. Why do proteins do this and what is the equilibrium between dynamics and structure during this short interaction? This also allows for a more accurate study of the mobility of loose proteins and their interactions with smaller molecules, such as drugs.


A different perspective on proteins


Ubbink: ‘The knowledge of protein complexes and protein dynamics that we amass, together with other researchers throughout the world, using NMR spectroscopy, will most probably lead to a change in the current standard biochemical perspective on proteins. Furthermore, I expect that a better understanding of proteins and their interactions will speed up and facilitate the development of drugs to treat all sorts of illnesses. This means that this research fits in very well with our Chemical Biology cluster, which works within the University research theme of the Science Base of Health. We also collaborate closely with biosynthetic chemists in this cluster.’

Leiden centre for paramagnetic NMR spectroscopy

With the purchase of the powerful 850 MHz spectrometer, the Leiden Science Faculty has at its disposal an impressive collection of NMR spectrometers, varying in power from 200 to 850 MHz. In combination with the new centre for Electron Nanoscopy (NeCEN), the Faculty has the required facilities for far-reaching fundamental research.

Also available to external users

Leiden University is a member of Medical Delta and Health-TIES and the Region of Knowledge (RoK). These networks also allow bio-science enterprises to make use of the Leiden facilities.

(19 June 2012)


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