ATP mimetics as inhibitors and probes of ATPases. (360G-Wellcome-093988_Z_10_Z)
The initial aim of this project is to synthesise a small library of ATP-mimetics and probe the heterogeneous ATP binding pockets of the 8 CCT subunits. The compounds will first be tested in steady state ATPase assays (Shimon et al; 2008) and an activity series assembled. Selected molecules would then be used in a chemical genetics screen against yeast CCT and ATP-site mutants in various of its subunits. Recent work in the Willison laboratory has led to an X-ray crystal structure for yeast CCT which is of sufficiently high resolution to guide the design of mutants. This will allow a level of understanding of this complex molecular machine which has not been achieved by any other approach. If time permits, the understanding gained of both the biology of CCT and the small molecules will be used to develop drug-like inhibitors of human CCT.
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Grant Details
| Amount Awarded | 153466 |
| Applicant Surname | Evans |
| Approval Committee | Neurosciences And Mental Health |
| Award Date | 2010-07-13T00:00:00+00:00 |
| Financial Year | 2009/10 |
| Grant Programme: Title | PhD Studentship (Basic & Clinical) |
| Internal ID | 093988/Z/10/Z |
| Lead Applicant | Miss Lindsay Evans |
| Partnership Value | 153466 |
| Planned Dates: End Date | 2014-09-30T00:00:00+00:00 |
| Planned Dates: Start Date | 2010-10-01T00:00:00+00:00 |
| Recipient Org: Country | United Kingdom |
| Region | Greater London |
| Sponsor(s) | Prof Paul Workman |