The transaldolase family : structure, function and evolution

The transaldolase gene family includes representatives from all kingdoms of life and the encoded enzymes are important for carbohydrate metabolism. The family can be divided into two subfamilies; Classical transaldolases and the MipB/TalC proteins. The reaction catalysed by the classical transaldolases is a reversible transfer of a dihydroxyacetone moiety from a ketose to an aldose sugar while members from the MipB/TaIC subfamily catalyse either this same reaction or a reversible cleavage of fructose 6-phosphate. The first part of these reactions is the formation of a covalent Schiff base intermediate of the substrate with an active site lysine, a feature common for all class 1 aldolases.

3D structures of members from both subfamilies have been determined by protein crystallography and they all show a single domain alpha/beta barrel fold common to all class I aldolases. Classical transaldolases from Escherichia coli and Homo sapiens are both dimers and show high overall similarity. Fructose 6-phosphate aldolase (FSA) from Escherichia coli, a member of the MipB/TalC subfamily, folds into a more compact barrel and is arranged as a decamer. The decamer is created through helix swapping of the C-terminal helix of FSA, the equivalent helix in the classical transaldolases covering the active site via a loop and being involved in the dimer interface.

Site-directed mutagenesis in combination with structural analysis was used to elucidate the mechanistic role of several active site residues in the classical Escherichia coli transaldolase. Fructose 6-phosphate aldolase catalyses a reversible cleavage instead of a transfer reaction and analysis of its active site compared to the classical transaldolase suggested explanations to this mechanistic difference.

List of scientific papers

I. Thorell S, Gergely P Jr, Banki K, Perl A, Schneider G (2000). "The three-dimensional structure of human transaldolase. " FEBS Lett 475(3): 205-8
https://pubmed.ncbi.nlm.nih.gov/10869557

II. Schorken U, Thorell S, Schurmann M, Jia J, Sprenger GA, Schneider G (2001). "Identification of catalytically important residues in the active site of Escherichia coli transaldolase. " Eur J Biochem 268(8): 2408-15
https://pubmed.ncbi.nlm.nih.gov/11298760

III. Thorell S, Schurmann M, Sprenger GA, Schneider G (2001). "Crystal structure of decameric fructose-6-phosphate aldolase from Escherichia coli reveals inter-subunit helix swapping as a structural basis for aasembly differences in the transaldolase family." (Manuscript)