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X-ray structural studies of substrate binding and mechanism of 5-aminolaevulinic acid dehydratase

Reference	B13781
Principal Investigator / Supervisor	Professor Jon Cooper
Co-Investigators / Co-Supervisors	Professor Peter Shoolingin-Jordan, Professor Martin Warren
Institution	University of Southampton
Department	Centre for Biological Sciences
Funding type	Research
Value (£)	180,112
Status	Completed
Type	Research Grant
Start date	01/11/2000
End date	31/10/2003
Duration	36 months

Abstract

5-Aminolaevulinate dehydratase (ALAD) catalyses one reaction of tetrapyrrole biosynthesis in which two 5- aminolaevulinic (ALA) molecules condense forming the pyrrole porphobilinogen. The X-ray structures of ALADs complexed with inhibitors and substrate define one of the two substrate binding sites where ALA forms a Schiff base with the enzyme. However, the second substrate binding site is still poorly defined and many aspects of the mechanism are uncertain. To address these issues we propose to analyse the bound structures of inhibitors designed to mimic both substrate moieties. We will analyse ternary complexes stabilised by reduction of the Schiff base or by the use of a suicide inhibitor and undertake freeze-trapping studies.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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