Fructose 1,6-bisphosphate Aldolase in Metabolism
Fructose 1,6-bisphosphate aldolase (FBA) (EC 188.8.131.52) catalyzes the reversible cleavage of fructose 1,6-bisphosphate (FBP) into the triose phosphates glyceraldehyde 3-phosphate (GADP) and dihydroxyacetone phosphate (DHAP); the catabolic glycolysis pathway utilizes the forward reaction, while the anabolic gluconeogenesis and Calvin cycle pathways utilize the reverse aldol condensation reaction (Rutter 1964). FBAs can be split into two classes based on the
Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections, First Edition. Edited by Brian Henderson.
© 2017 John Wiley & Sons, Inc. Published 2017 by John Wiley & Sons, Inc.
reaction mechanism employed (Perham 1990). Class I FBAs form a Schiff base intermediate between a highly conserved active site lysine and a substrate carbonyl group. Class I FBAs, which often form tetramers, are commonly found in higher animals and plants, but rarely in bacteria (Thomson et al. 1998; Sauve and Sygusch 2001). In bacteria, class II FBAs are more common; these require an active site divalent metal ion, often zinc, for enzymatic activity (Hall et al. 1999; Zgiby et al. 2000, 2002). Only a few organisms, for example Escherichia coli, contain both classes of FBAs (Stribling and Perham 1973). Class II FBAs can be further divided into type A and type B based on their amino acid sequences (Plaumann et al. 1997); class IIA enzymes are generally dimeric, while class IIB enzymes may be dimeric, tetrameric, or octameric (Sauve and Sygusch 2001; Nakahara et al. 2003). Both class I and class II aldolases catalyze the same enzymatic reaction and adopt a common folding topology (a triose phosphate isomer- ase or TIM barrel (a/p)8 barrel). However, they do not share significant amino acid sequence homology or conserved catalytic residues and the location of their active sites within the TIM barrel is distinct, suggesting that similarities of the tertiary structures of the two classes of enzyme are a result of convergent evolution (Marsh and Lebherz 1992; Blom et al. 1996; Nagano et al. 2002). Indeed, aldolases found in some archaeal species which belong to class I (based on their reaction mechanism) lack significant amino acid sequence homology with either class I or class II aldolases (Siebers et al. 2001). Bifunctional fructose 1,6-bispho- sphate aldolase/phosphatase enzymes, which are a unique class of proteins with both FBP aldolase and FBP phosphatase activity, have also been found in archaea and some rare thermophilic and autotrophic bacteria (Say and Fuchs 2010).