In situ crystallography as an emerging method for structure solution of membrane proteins: the case of CCR2A
Robert Chenga b, Chia‐Ying Huangc d, Michael Henniga b, Herbert Nare f, Gisela Schnappe f✉
- aPARK innovAARE leadXpro AG Villigen Switzerland
- bPARK innovAARE, leadXpro AG, Villigen, Switzerland
- cSwiss Light Source Paul Scherrer Institute Villigen Switzerland
- dSwiss Light Source, Paul Scherrer Institute, Villigen, Switzerland
- eBoehringer Ingelheim Pharma GmbH &
- fCo. KG Biberach Germany
- ✉Corresponding author
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Abstract
The in meso in situ serial X-ray crystallization method (Huang et al., (2015) Acta Crystallogr D Biol Crystallogr 71, 1238) combines lipid cubic phase crystallization, direct freezing of the crystallization droplet without handling of the crystals, and data collection in situ. Recently, this method was used to overcome the mechanical fragility of crystals which enabled the X-ray structure determination of chemokine receptor 2A (Apel et al., (2019) Structure 27, 427) at 2.7 Å resolution. The CCR2 structure provides the structural basis for ligand selectivity of CCR2 against chemokine receptor 5 and provides insights into the residence time of MK-0812 analogs based on molecular dynamics simulations. These findings offer new opportunities for drug discovery targeting chemokine receptors.
TL;DRThe CCR2 structure provides the structural basis for ligand selectivity of C CR2 against chemokine receptor 5 and provides insights into the residence time of MK‐0812 analogs based on molecular dynamics simulations. (Semantic Scholar)