Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633417
Title: Structural & biochemical characterisation of Cdc25C : a dual specificity phosphatase
Author: Akhtar, Nazia
ISNI:       0000 0004 5346 1038
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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Abstract:
The dual specificity Cdc25 phosphatases regulate mitosis and are expressed in eukaryotes. Cdc25 phosphatases have an active site motif, HCX5R, in common with other phosphatases. However, unlike the classical tyrosine phosphatases, they can dephosphorylate phospho-threonine in addition to phospho-tyrosine and have a much shallower active site. Increased expression of Cdc25 is correlated with poor prognosis in a range of cancers. In particular, increased expression of Cdc25C has been associated with prostate cancer making this protein an attractive target for drug discovery. However, drug discovery for these proteins has been hampered due to the shallow nature of the active site, difficulty in identifying specific inhibitors and toxicity. The thesis aim was to structurally and biochemically characterize Cdc25C using a range of techniques which include NMR, SAXS and X-ray crystallography in order to aid future drug design. The Characterisation of the Cdc25C full length revealed the regulatory domain to be intrinsically disordered and flexible. Construct and solution conditions were optimised to improve the solubility of the Cdc25C catalytic domain. Although, the \(^1\)H, \(^1\)\(^5\)N HSQC was well dispersed backbone assignments proved to be refractory. From a panel of inhibitors tested a few were shown to bind via WaterLOGSY and \(^1\)H-\(^1\)\(^5\)N HSQC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.633417  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
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