Not sure if there was a proper consultation on this, but the 3D printer has a name now.
05
Mar
2023
News
22
Feb
2023
Going 3D, really 3D
After 20+ years of determining atomic level structures of proteins in three dimensions, we are going properly 3D. Our Prusa i3 MKS3+ has arrived!
01
Feb
2023
One of those weeks
HPLC plays up with random UV peaks, fraction collector tries to fail its calibration, centrifuge bottles crack with half of mammalian expression culture lost, fluorescent detector cuts off randomly.
And it’s only a Wednesday.
Panton Arms, here we come.
18
Jan
2023
Part II projectiles have arrived
Welcome to Sarah and Bocheng for joining the group for their part II projects (third year undergraduate project in normal terminology), under the supervision of Shiv and Emma, respectively.
22
Nov
2021
Welcome to new members
Welcome to new lab members Emma, Gwen, Aleks and Miha!
25
Sep
2017
Paul & co’s work on CK2α inhibition highlighted
Dan Erlanson has highlighted our project on Ck2α inhibitor development in his Practical Fragments blog “Fragment Linking to selective Ck2 inhibitor“.
This a project we have done in close collaboration with David Spring’s group at the Department of Chemistry. The story started from a serendipitous observation that a fragment expected to bind on the top of the N-lobe of CK2α, on the interaction site with scaffolding protein Ck2β bound in a number of different sites on the kinase, including in a new pocket close to the ATP binding site of the kinase. This previously unidentified site was observed only thanks to a new crystal form Paul had obtained. In this crystal form, the so-called αD helix was mobile enough to be displaced by a fragment that, soaked at high concentration, found a new home in the very hydrophobic pocket that the displacement of the helix revealed. After some optimisation of the fragment and a crystallographic screen to identify ATP-site binding “war heads”, Claudia and others in the Spring lab were able to create the linked molecule CAM4066.
The main story was published in Chemical Science and the detailed description of the design process came out this year in Bioorganic and Medicinal Chemistry.
If interested more in this story, do check in Youtube some of the movies Paul has made from this project:
Optimisation of the fragment in the aD pocket
Growth of the linker from the aD site to the active site
And it should not go forgotten that all the work has been guided continuous crystallographic assessement of the process, with ~30 unique crystal structures in the two papers: 5CVH (3D view), 5CVG (3D view), 5CVF (3D view), 5CU3 (3D view), 5CU4 (3D view), 5CU6 (3D view), 5CSH (3D view), 5CSP (3D view), 5CSV (3D view), 5CSH (3D view), 5CS6 (3D view), 5CLP (3D view), 5MMF (3D view ), 5MMR (3D view ), 5MO5 (3D view ), 5MO6 (3D view ), 5MO7 (3D view ), 5MO8 (3D view ), 5MOD (3D view ), 5MOE (3D view ), 5MOH (3D view ), 5MOT (3D view ), 5MOV (3D view ), 5MOW (3D view ), 5CU0 (3D view ), 5CU2 (3D view ), 5CT0 (3D view ), 5CTP (3D view ), 5CX9 (3D view ).
And there is more to come! Keep your eyes open.