Publications authored by leadXpro scientists
First Cryo-EM structure of the human TRPV4 ion-channel in the open conformation, in complex with an agonist.
In partnership with Bayer, leadXpro has generated protein and solved the cryo-EM structure of human TRPV4 in complex with the agonist 4α-PDD, providing novel information about agonist binding to this important drug target.
In a partnership with Boehringer Ingelheim, leadXpro generated protein and provided the X-ray structure data to advance their drug discovery programs on CCR2, a chemokine receptor target.
leadXpro, PSI, ETH and Sosei Heptares scientists present sensitivity improvements for XFEL measurements by using long wavelength pulses and improvements in data evaluation.
Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity
The publication provides evidence implicating suppression of adaptive and innate immunity by adenosine as a mechanism for immune evasion by tumors. Inhibition of adenosine signaling through selective small molecule inhibition of A R using AZD4635 restores T cell function
cross-presentation by CD103+ DCs resulting in antitumor immunity.
This crystallography review summarizes the current main strategies in sample delivery and their respective pros and cons, as well as some future direction.
In situ crystallography as an emerging method for structure solution of membrane proteins: the case of CCR2A
The in meso in situ serial X-ray crystallization method enables structure determination of very fragile crystals.
leadXpro CEO Michael Hennig contributes a chapter about the progress of structure biology in drug discovery
Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists
Two independent structures of CCR2A in complex with the orthosteric antagonist MK-0812 were solved, confirming the importance of residue E2917.39 for antagonist binding. Structural modeling of pyrimidine amide antagonists showed an interaction with the non-conserved H1213.33, leading to a significant selectivity over CCR5, suggesting strategies for highly selective CCR2 antagonist design.