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X-ray structure analysis of 5-aminolaevulinate dehydratase

Reference	B06948
Principal Investigator / Supervisor	Professor Jon Cooper
Co-Investigators / Co-Supervisors	Professor Peter Shoolingin-Jordan, Professor Stephen Wood
Institution	University of Southampton
Department	Centre for Biological Sciences
Funding type	Research
Value (£)	159,398
Status	Completed
Type	Research Grant
Start date	01/11/1996
End date	01/11/1999
Duration	36 months

Abstract

5-aminolaevulinic acid dehydratase (ALAD) catalyses the formation of the haem precursor, porphobilinogen, by a novel reaction involving the dimerisation of two identical molecules of 5-aminolaevulinic acid. ALAD is an unusual metalloaldolase with catalytic (alpha) and structural (beta) metal ions which also utilises a Schiff base during catalysis. The X-ray structure of ALADs from Escherichia coli and yeast will be solved by isomorphous replacement and multiwavelength anomalous dispersion (MAD) methodologies. Native data have been obtained at 2 Angstroms resolution and a promising SIR map based on a 2 site lead derivative is already available. The two substrate binding sites (A and P sites) will be identified using substrate, inhibitor and product complexes. The identity of the catalytic groups and alpha- and beta-metal binding ligands will be defined by a combination of X-ray crystallography, site-directed mutagenesis and enzyme kinetics and by comparison between the zinc-dependent bacterial enzyme and the magnesium-dependent plant enzyme structures.

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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