Region Directed Mutagenesis of Varicella-Zoster Virus Thymidylate Synthase

Boffey, Judith (1998) Region Directed Mutagenesis of Varicella-Zoster Virus Thymidylate Synthase. PhD thesis, University of Glasgow.

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Thymidylate synthase (TS) catalyses the reductive methylation of deoxyuridine monophosphate by 5,10-methylenetetrahydrofolate to produce thymidylate and dihydrofolate. In the reaction the enzyme is present initially as an open complex that closes down progressively as ligands bind. The binary complex which is formed as the substrate dUMP binds has an active site that is open and structurally very close to the unliganded state. It is upon binding of the folate cofactor that structural changes occur and the enzyme forms a closed ternary structure. In contrast to the movements of large domains seen in other proteins upon ligand binding, the changes in TS involves segmental accommodation in which segments of secondary structural elements all move in concert towards the active site. The two largest shifts involve the C-terminus and DRTG loop which moves 4A to close over the active site.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: J H Sharpe-Subak
Keywords: Virology, Biochemistry
Date of Award: 1998
Depositing User: Enlighten Team
Unique ID: glathesis:1998-74474
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 18:11
Last Modified: 27 Sep 2019 18:11

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