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Structure of Tagatose-1,6-bisphosphate Aldolase. Insight into chiral discrimination, mechanism, and specificity of class II aldolases

Hall, D.R., Bond, C.S., Leonard, G.A., Watt, C.I., Berry, A. and Hunter, W.N. (2002) Structure of Tagatose-1,6-bisphosphate Aldolase. Insight into chiral discrimination, mechanism, and specificity of class II aldolases. Journal of Biological Chemistry, 277 (24). pp. 22018-22024. ISSN 1083-351X

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Abstract

Tagatose-1,6-bisphosphate aldolase (TBPA) is a tetrameric class II aldolase that catalyzes the reversible condensation of dihydroxyacetone phosphate with glyceraldehyde 3-phosphate to produce tagatose 1,6-bisphosphate. The high resolution (1.45 Å) crystal structure of the Escherichia coli enzyme, encoded by the agaY gene, complexed with phosphoglycolohydroxamate (PGH) has been determined. Two subunits comprise the asymmetric unit, and a crystallographic 2-fold axis generates the functional tetramer. A complex network of hydrogen bonds position side chains in the active site that is occupied by two cations. An unusual Na(+) binding site is created using a interaction with Tyr(183) in addition to five oxygen ligands. The catalytic Zn(2+) is five-coordinate using three histidine nitrogens and two PGH oxygens. Comparisons of TBPA with the related fructose-1,6-bisphosphate aldolase (FBPA) identifies common features with implications for the mechanism. Because the major product of the condensation catalyzed by the enzymes differs in the chirality at a single position, models of FBPA and TBPA with their cognate bisphosphate products provide insight into chiral discrimination by these aldolases. The TBPA active site is more open on one side than FBPA, and this contributes to a less specific enzyme. The availability of more space and a wider range of aldehyde partners used by TBPA together with the highly specific nature of FBPA suggest that TBPA might be a preferred enzyme to modify for use in biotransformation chemistry.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Molecular and Cellular Biology (Leeds)
Depositing User: Repository Officer
Date Deposited: 13 Mar 2006
Last Modified: 07 Jun 2014 02:07
Published Version: http://www.jbc.org./cgi/content/full/277/24/22018
Status: Published
Refereed: Yes
Identification Number: 10.1074/jbc.M202464200
URI: http://eprints.whiterose.ac.uk/id/eprint/605

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