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X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase

Nature Structural Biology volume 4, pages 1025–1031 (1997)Cite this article

Abstract

5-Aminolaevulinate dehydratase (ALAD) is a homo-octameric metallo-enzyme that catalyses the formation of porphobilinogen from 5-aminolaevulinic acid. The structure of the yeast enzyme has been solved to 2.3 Å resolution, revealing that each subunit adopts a TIM barrel fold with a 39 residue N-terminal arm. Pairs of monomers wrap their arms around each other to form compact dimers and these associate to form a 422 symmetric octamer. All eight active sites are on the surface of the octamer and possess two lysine residues (210 and 263), one of which, Lys 263, forms a Schiff base link to the substrate. The two lysine side chains are close to two zinc binding sites one of which is formed by three cysteine residues (133,135 and 143) while the other involves Cys 234 and His 142. ALAD has features at its active site that are common to both metallo- and Schiff base-aldolases and therefore represents an intriguing combination of both classes of enzyme. Lead ions, which inhibit ALAD potently, replace the zinc bound to the enzyme's unique triple-cysteine site.

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Author notes

  1. Paul Spencer

    Present address: Center for Biological NMR, Department of Chemistry, Texas A & M University, College Station, Texas, 77843, USA

Authors and Affiliations

  1. Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, S016 7PX, UK

    Peter T. Erskine, Richard Lambert, Gareth Lewis, M. Sarwar, Peter M. Shoolingin-Jordan, Steve P. Wood & Jon B. Cooper

  2. Department of Molecular Genetics, Institute of Ophthalmology, University College London, Bath Street, London, EC1V 9EL, UK

    Natalie Senior, Sarah Awan & Martin J. Warren

  3. Department of Crystallography, Birkbeck College, University of London, London, WC1E 7HX, UK

    Ian J. Tickle

  4. Zeneca Agrochemicals, Jealotts Hill Research Station, Bracknell, Berkshire, RG12 6EY, UK

    Paul Thomas

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Erskine, P., Senior, N., Awan, S. et al. X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase. Nat Struct Mol Biol 4, 1025–1031 (1997). https://doi.org/10.1038/nsb1297-1025

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