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5-Aminolaevulinic Acid Dehydratase, Porphobilinogen Deaminase and Uroporphyrinogen III Synthase

  • Chapter
Tetrapyrroles

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The three enzymes 5-aminolaevulinic acid dehydratase (ALAD, E.C.4.2.1.24; some times referred to as porphobilinogen synthase), porphobilinogen deaminase (EC 4.3.1.8; also known as hydroxymethylbilane synthase) and uroporphyrinogen III synthase (U3S; E.C.4.2.1.75) together convert 5-aminolaevulinic acid (ALA) into uroporphyrinogen III, from which all tetrapyrroles are synthesized. The X-ray structures of several ALADs have been determined showing that the enzyme forms a large homo-octameric structure with all eight active sites on the outer surface. Each subunit adopts the TIM barrel fold with an N-terminal arm which forms extensive inter-subunit interactions. The active site of each subunit is located in a pronounced cavity formed by loops at the C-terminal ends of the strands forming the TIM barrel. Current proposals for the catalytic mechanism involve the binding of both substrate moieties by formation of Schiff bases with two invariant active site lysine residues. Structural studies of porphobilinogen deaminase have shown that the enzyme has three domains, two of which show a strong structural resemblance to a number of periplasmic binding proteins. The reaction catalysed by uroporphyrinogen III synthase involves cyclization and ring inversion, predicted to proceed through a spirocyclic intermediate. X-ray structures of the enzyme from humans and a thermophilic bacterium have enabled models of the catalytic process to be proposed.

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Authors and Affiliations

  1. Department of Biochemistry, University of Utah, Salt Lake City, Utah, USA

    Heidi L. Schubert

  2. Laboratory for Protein Crystallography Centre for Amyloidosis and Acute Phase Proteins, UCL Department of Medicine, London, UK

    Peter T. Erskine

  3. School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampto, SO16 7PX, UK

    Jonathan B. Cooper

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  1. Heidi L. Schubert
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  2. Peter T. Erskine
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  3. Jonathan B. Cooper
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Correspondence to Jonathan B. Cooper .

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© 2009 Landes Bioscience and Springer Science+Business Media.

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Schubert, H.L., Erskine, P.T., Cooper, J.B. (2009). 5-Aminolaevulinic Acid Dehydratase, Porphobilinogen Deaminase and Uroporphyrinogen III Synthase. In: Tetrapyrroles. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78518-9_3

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