ISSN:
1399-0047
Source:
Crystallography Journals Online : IUCR Backfile Archive 1948-2001
Topics:
Chemistry and Pharmacology
,
Geosciences
,
Physics
Notes:
MAD experiments attempting to solve the structure of 5-aminolaevulinic acid dehydratase using Zn and Pb edges are described. The data obtained proved insufficient for a complete structure solution but were invaluable in subsequent identification of metal-binding sites using anomalous difference Fourier analyses once the structure of the enzyme had been solved. These sites include the highly inhibitory substitution of an enzymic cofactor Zn2+ ion by Pb2+ ions, which represents a major contribution towards understanding the molecular basis of lead poisoning. The MAD data collected at the Pb edge were also used with isomorphous replacement data from the same Pb co-crystal and a Hg co-crystal to provide the first delineation of the enzyme's quaternary structure. In this MADIR analysis, the Hg co-crystal data were treated as native data. Anomalous difference Fouriers were again used, revealing that Hg2+ had substituted for the same Zn2+ cofactor ion as had Pb2+, a finding of fundamental importance for the understanding of mercury poisoning. In addition, Pt2+ ions were found to bind at the same place in the structure. The refined structures of the Pb- and the Hg-complexed enzymes are presented at 2.5 and 3.0 Å resolution, respectively.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1107/S0907444900000597
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