Coates, Leighton, Beaven, Gordon, Erskine, Peter T., Beale, Samuel I., Avissar, Yael J., Gill, Raj, Mohammed, Fiyaz, Wood, Steve P., Shoolingin-Jordan, Peter and Cooper, Jon P.
The x-ray structure of the plant like 5-aminolaevulinic acid dehydratase from chlorobium vibrioforme complexed with the inhibitor laevulinic acid at 2.6 A° resolution.
Journal of Molecular Biology, 342, (2), . (doi:10.1016/j.jmb.2004.07.007).
5-Aminolaevulinic acid dehydratase (ALAD), an early enzyme of the
tetrapyrrole biosynthesis pathway, catalyses the dimerisation of 5-
aminolaevulinic acid to form the pyrrole, porphobilinogen. ALAD from
Chlorobium vibrioforme is shown to form a homo-octameric structure with
422 symmetry in which each subunit adopts a TIM-barrel fold with a 30
residue N-terminal arm extension. Pairs of monomers associate with their
arms wrapped around each other. Four of these dimers interact principally
via their arm regions to form octamers in which each active site is located
on the surface. The active site contains two invariant lysine residues (200
and 253), one of which (Lys253) forms a Schiff base link with the bound
substrate analogue, laevulinic acid. The carboxyl group of the laevulinic
acid forms hydrogen bonds with the side-chains of Ser279 and Tyr318. The
structure was examined to determine the location of the putative active-site
magnesium ion, however, no evidence for the metal ion was found in the
electron density map. This is in agreement with previous kinetic studies
that have shown that magnesium stimulates but is not required for activity.
A different site close to the active site flap, in which a putative magnesium
ion is coordinated by a glutamate carboxyl and five solvent molecules may
account for the stimulatory properties of magnesium ions on the enzyme.
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