Fersht
Group
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We
use an amalgam
of protein engineering, structural biology, biophysics and
chemistry to
study the structure, activity, stability and folding of
proteins, and
the role of protein misfolding and instability in cancer
and disease.
We focus on how mutation affects proteins in the cell
cycle,
particularly the tumour suppressor p53, in order to design
novel
anti-cancer drugs that function by restoring the activity
of mutated
proteins.
Cancer is a disease of mutation, and the most commonly mutated protein by far is the tumour suppressor p53. This protein, sometimes called the "Guardian of the Genome", does not only lead the major defence of the cell against cancer but also has a wide range of roles in the cell cycle, from fertility to senescence. It has a very complicated structure, comprised of two folded and three intrinsically disordered domains in each of its monomers that associate to form dimers and tetramers. It is a major hub protein and interacts with a host of other proteins involved in the cell cycle. We discovered that about 30% of oncogenic mutants of p53 are just temperatures sensitive and can, in theory, be rescued by small molecules. |
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Tumour
Suppressor p53
Structural Biology and Drug Discovery |
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Alan Fersht MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge CB2 0QH Email alan@mrc-lmb.cam.ac.uk |
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