Helmholtz Zentrum Berlin

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BESSY • The ideal microscope for space and time

business as (un)usual

authored 2 years ago:

Function follows form: how BESSY II helps with drug design

Proteins or enzymes play a crucial role in many processes within the body. They can be huge molecules, sometimes several thousand atoms large. And they can have really complex shapes. We need to know every wrinkle or fold, since this is deciding how they interact with other molecules, for instance drugs. This is no trivial task: In a first step, we need to grow protein crystals, to arrange the large proteins neatly in an ordered lattice. This already is an art in itself. In the next step, we can use the MX-Beamlines at BESSY II to analyse the protein crystals and to get information about their 3D shape. Since their installment in 2003, more than 2000 protein structures have been solved at the MX Beamlines.

Sirt3

This image shows the 1000. structure, which was solved in 2013 by the group of Clemens Steegborn, Bayreuth University. It is an enzyme, called SIrt3 (light grey). Another molecule, Ex-527 (colored structure), has docked at Sirt3. This result is of interest for medical research and drug design: Sirtuins are really important in the human body, they regulate metabolism, stress responses and aging processes in the body and even the onset of cancer. With their study, Steegborn and his group have explained how the activity of Sirt3 can be suppressed by the molecule Ex-527 (PNAS, 2013: Ex-527 inhibits Sirtuins). “If we are able to use this to specifically inhibit the activity of individual sirtuins, then this could be one approach to an effective therapy with only minimal side-effects,” Steegborn reports optimistically.