Structures of Shikimate dehydrogenase AroE and its paralog YdiB: a common structural framework for different activities

Michel, G., Roszak, A.W., Sauve, V., Maclean, J., Matte, A., Coggins, J.R., Cygler, M. and Lapthorn, A.J. (2003) Structures of Shikimate dehydrogenase AroE and its paralog YdiB: a common structural framework for different activities. Journal of Biological Chemistry, 278, pp. 19463-19472. (doi: 10.1074/jbc.M300794200)

Full text not currently available from Enlighten.

Abstract

Shikimate dehydrogenase catalyzes the fourth step of the shikimate pathway, the essential route for the biosynthesis of aromatic compounds in plants and microorganisms. Absent in metazoans, this pathway is an attractive target for nontoxic herbicides and drugs. Escherichia coli expresses two shikimate dehydrogenase paralogs, the NADP-specific AroE and a putative enzyme YdiB. Here we characterize YdiB as a dual specificity quinate/shikimate dehydrogenase that utilizes either NAD or NADP as a cofactor. Structures of AroE and YdiB with bound cofactors were determined at 1.5 and 2.5 Å resolution, respectively. Both enzymes display a similar architecture with two α/β domains separated by a wide cleft. Comparison of their dinucleotide-binding domains reveals the molecular basis for cofactor specificity. Independent molecules display conformational flexibility suggesting that a switch between open and closed conformations occurs upon substrate binding. Sequence analysis and structural comparison led us to propose the catalytic machinery and a model for 3-dehydroshikimate recognition. Furthermore, we discuss the evolutionary and metabolic implications of the presence of two shikimate dehydrogenases in E. coli and other organisms.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lapthorn, Dr Adrian and Coggins, Professor John and Roszak, Dr Aleksander
Authors: Michel, G., Roszak, A.W., Sauve, V., Maclean, J., Matte, A., Coggins, J.R., Cygler, M., and Lapthorn, A.J.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Science and Engineering > School of Chemistry
College of Medical Veterinary and Life Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:12 March 2003

University Staff: Request a correction | Enlighten Editors: Update this record