Abstract
Transaldolase catalyzes transfer of a dihydroxyacetone moiety from a ketose donor to an aldose acceptor. During catalysis, a Schiff-base intermediate between dihydroxyacetone and the epsilon-amino group of a lysine residue at the active site of the enzyme is formed. This Schiff-base intermediate has been trapped by reduction with potassium borohydride, and the crystal structure of this complex has been determined at 2.2 A resolution. The overall structures of the complex and the native enzyme are very similar; formation of the intermediate induces no large conformational changes. The dihydroxyacetone moiety is covalently linked to the side chain of Lys 132 at the active site of the enzyme. The Cl hydroxyl group of the dihydroxyacetone moiety forms hydrogen bonds to the side chains of residues Asn 154 and Ser 176. The C3 hydroxyl group interacts with the side chain of Asp 17 and Asn 35. Based on the crystal structure of this complex a reaction mechanism for transaldolase is proposed.
Full Text
The Full Text of this article is available as a PDF (1.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banki K., Perl A. Inhibition of the catalytic activity of human transaldolase by antibodies and site-directed mutagenesis. FEBS Lett. 1996 Jan 8;378(2):161–165. doi: 10.1016/0014-5793(95)01446-2. [DOI] [PubMed] [Google Scholar]
- Gamblin S. J., Cooper B., Millar J. R., Davies G. J., Littlechild J. A., Watson H. C. The crystal structure of human muscle aldolase at 3.0 A resolution. FEBS Lett. 1990 Mar 26;262(2):282–286. doi: 10.1016/0014-5793(90)80211-z. [DOI] [PubMed] [Google Scholar]
- Gefflaut T., Blonski C., Perie J., Willson M. Class I aldolases: substrate specificity, mechanism, inhibitors and structural aspects. Prog Biophys Mol Biol. 1995;63(3):301–340. doi: 10.1016/0079-6107(95)00008-9. [DOI] [PubMed] [Google Scholar]
- Hester G., Brenner-Holzach O., Rossi F. A., Struck-Donatz M., Winterhalter K. H., Smit J. D., Piontek K. The crystal structure of fructose-1,6-bisphosphate aldolase from Drosophila melanogaster at 2.5 A resolution. FEBS Lett. 1991 Nov 4;292(1-2):237–242. doi: 10.1016/0014-5793(91)80875-4. [DOI] [PubMed] [Google Scholar]
- Jia J., Huang W., Schörken U., Sahm H., Sprenger G. A., Lindqvist Y., Schneider G. Crystal structure of transaldolase B from Escherichia coli suggests a circular permutation of the alpha/beta barrel within the class I aldolase family. Structure. 1996 Jun 15;4(6):715–724. doi: 10.1016/s0969-2126(96)00077-9. [DOI] [PubMed] [Google Scholar]
- Lai C. Y., Chen C., Tsolas O. Isolation and sequence analysis of a peptide from the active site of transaldolase. Arch Biochem Biophys. 1967 Sep;121(3):790–797. doi: 10.1016/0003-9861(67)90068-9. [DOI] [PubMed] [Google Scholar]
- Lai C. Y., Oshima T. Studies on the structure of rabbit muscle aldolase. 3. Primary structure of the BrCN peptide containing the active site. Arch Biochem Biophys. 1971 May;144(1):363–374. doi: 10.1016/0003-9861(71)90489-9. [DOI] [PubMed] [Google Scholar]
- Morris A. J., Tolan D. R. Site-directed mutagenesis identifies aspartate 33 as a previously unidentified critical residue in the catalytic mechanism of rabbit aldolase A. J Biol Chem. 1993 Jan 15;268(2):1095–1100. [PubMed] [Google Scholar]
- Sprenger G. A., Schörken U., Sprenger G., Sahm H. Transaldolase B of Escherichia coli K-12: cloning of its gene, talB, and characterization of the enzyme from recombinant strains. J Bacteriol. 1995 Oct;177(20):5930–5936. doi: 10.1128/jb.177.20.5930-5936.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sygusch J., Beaudry D., Allaire M. Molecular architecture of rabbit skeletal muscle aldolase at 2.7-A resolution. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7846–7850. doi: 10.1073/pnas.84.22.7846. [DOI] [PMC free article] [PubMed] [Google Scholar]