Birth of the Cool: Multitemperature Multiconformer X-Ray Crystallography and Allostery
Protein conformational landscapes are complex and predicting the conformational response to physiologically relevant perturbations like mutation or small molecule binding is a major challenge. Often, functionally-relevant states are nearly isoenergetic (separated in energy by a few kT, or less), meaning that at physiological temperatures, multiple conformational states populate the ensemble. Using newly developed multiconformer models of X-ray data, we have shown how population shifts can result from temperature perturbation. Our experience over multiple systems has demonstrated that temperature sensitive conformational states are the same ones used by evolution to create new functions, by small molecules in creating new binding sites, and by enzymes to transit through a catalytic cycle. Using an easily controllable physical perturbation (temperature) to predict the conformational response to physiological perturbations suggests the specific conformations to enforce at allosteric sites to achieve long-range control over protein activity.
Date:
19 September 2016, 15:00 (Monday, -2nd week, Michaelmas 2016)
Venue:
Richard Doll Building, Old Road Campus OX3 7LF
Venue Details:
Lecture theatre
Speaker:
Dr James Fraser (UCSF)
Organising department:
Structural Genomics Consortium
Organiser:
Natsumi Astley (University of Oxford )
Organiser contact email address:
natsumi.astley@sgc.ox.ac.uk
Host:
Prof Frank von Delft (SGC, University of Oxford)
Part of:
CMD Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Natsumi Astley
