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)
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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 |
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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 |
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