X-ray structure of a putative reaction intermediate of 5-aminolaevulinic acid dehydratase

Description/Abstract

The X-ray structure of yeast 5-aminolaevulinic acid dehydratase,
in which the catalytic site of the enzyme is complexed with a
putative cyclic intermediate composed of both substrate moieties,
has been solved at 0.16 nm (1.6 Å) resolution. The cyclic intermediate
is bound covalently to Lys(263) with the amino group of
the aminomethyl side chain ligated to the active-site zinc ion in
a position normally occupied by a catalytic hydroxide ion. The
cyclic intermediate is catalytically competent, as shown by its
turnover in the presence of added substrate to form porphobilinogen.
The findings, combined with those of previous studies,
are consistent with a catalytic mechanism in which the C–C bond
linking both substrates in the intermediate is formed before the
C–N bond.