our papers

Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists

Anna-Katharina Apel, Robert K.Y. Cheng, Christofer S. Tautermann, Michael Brauchle, Chia-Ying Huang, Alexander Pautsch, Michael Hennig, Herbert Nar, Gisela Schnapp 

We determined two crystal structures of the chemokine receptor CCR2A in complex with the orthosteric antagonist MK-0812. Full-length CCR2A, stabilized by rubredoxin and a series of five mutations were resolved at 3.3 Å. An N- and C-terminally truncated CCR2A construct was crystallized in an alternate crystal form, which yielded a 2.7 Å resolution structure using serial synchrotron crystallography. Our structures provide a clear structural explanation for the observed key role of residue E2917.39 in high-affinity binding of several orthosteric CCR2 antagonists. By combining all the structural information collected, we generated models of co-structures for the structurally diverse pyrimidine amide class of CCR2 antagonists. Even though the representative Ex15 overlays well with MK-0812, it also interacts with the non-conserved H1213.33, resulting in a significant selectivity over CCR5. Insights derived from this work will facilitate drug discovery efforts directed toward highly selective CCR2 antagonists with potentially superior efficacy.

Interview of leadXpro's CEO Michael Hennig by the journal EuropeanCEO

Our CEO was interviewed by the journal “European CEO“. In the Summer edition of 2018 a number of emerging CEOs from Europe based companies are introduced. Michael Hennig’s interview “Taking the lead” emphasizes facts about the core business of leadXpro, the impact of membrane proteins as drug targets and the key advantages leadXpro’s technologies provide to drug discovery and the creation of differentiating medicines.


Read the article here

Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons

T. Weinert, N. Olieric, R. Cheng, S. Brünle et al. 

Nature Communications 8:542 (2017)

The authors show that serial millisecondcrystallography (SMX) at synchrotrons allows fast, straightforward structure determination at room-temperature for large soluble macromolecular complexes as well as membrane proteins. Using SMX, a much larger dose can be distributed over many crystals, resulting in higher resolution structures with less-radiation damage compared with classical room-temperature methods. Modern fast frame rate detectors produce results of excellent quality, making even native SAD phasing possible in less than a single 8-h synchrotron shift. Using ultra high frame rate detectors and next-generation diffraction-limited sources, time-resolved measurements in the micro- and perhaps nanosecond range may become possible at synchrotrons. Given the comparatively simple sample preparation, data collection, data processing and its great potential for automation, the authors believe that SMX is the method of choice for room-temperature structure determination and fragment screening approaches.

X-ray Free Electron Laser: Opportunities for drug discovery

Cheng R., Abela R., Hennig M.

The authors demonstrate that XFEL structure determination has matured to reality and point out the many advantages of the technology: Unmet brilliance and focus, femtosecond pulses and low/no radiation damage and measurement at room temperature allow structure determinations of challenging systems like membrane proteins, investigation of time-resolved ligand binding, new structural insights due to room temperature and full automation of crystal diffraction experiments.

Structural biology: doors open at the European XFEL

Vivien Marx

A technology feature by Nature Methods’ technology editor Vivien Marx about free electron lasers to comment on the opening of the European X-ray Free Electron Laser (EuXFEL) in Hamburg, Germany. One paragraph of the article refers to the SwissFEL (opened in December 2016) and the applied research at this instrument that will be facilitated by leadXpro AG.